Secondary literature sources for FH
The following references were automatically generated.
- Osborne LR
- 'Forkhead' gene expression balanced on a knife-edge.
- Trends Mol Med. 2001; 7: 51-51
- Goldstein B, Leviten MW, Weisblat DA
- Dorsal and snail homologs in leech development.
- Dev Genes Evol. 2001; 211: 329-37
- Display abstract
As part of an examination of how developmental mechanisms such as axis specification, cell fate specification, and segmentation have evolved, we have cloned homologs of the Drosophila melanogaster genes dorsal and snail from the glossiphoniid leech Helobdella robusta. Sequences from one dorsal-class gene (Hro-dl) and two snail-class genes (Hro-sna1 and Hro-sna2) were identified. Polyclonal antibodies were raised against the most conserved domains of HRO-DL and HRO-SNA1. Nuclear staining appeared for both proteins in mid-embryogenesis, in mesodermal and ectodermal precursors. During segmentation, segmentally iterated stripes of cells with strong HRO-DL staining appeared. The stripes of HRO-DL staining were first concentrated in the cytoplasm of cells, and later in the nuclei. Around this time, HRO-SNA levels also appeared in nuclei in segmentally iterated stripes. The localization of HRO-DL and HRO-SNA proteins raise the possibility that these genes are part of a conserved genetic pathway that, instead of specifying the dorsoventral axis and the mesoderm as in flies, might play a role in the diversification of cell types within segment primordia during leech development.
- Miura N
- [Developmental roles of forkhead genes in organogenesis]
- Tanpakushitsu Kakusan Koso. 2001; 46: 26-35
- Greaves S
- Migration on the borderline.
- Nat Cell Biol. 2001; 3: 45-45
- Kietzmann T, Cornesse Y, Brechtel K, Modaressi S, Jungermann K
- Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha-subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver.
- Biochem J. 2001; 354: 531-7
- Display abstract
The cDNAs of three hypoxia-inducible factor (HIF) alpha-subunits were cloned from RNA of primary rat hepatocytes by reverse transcriptase PCR. All three cDNAs encoded functionally active proteins, of 825, 874 and 662 amino acids. After transfection they were able to activate luciferase activity of a luciferase gene construct containing three HIF-responsive elements. The mRNAs of the rat HIF alpha-subunits were expressed predominantly in the perivenous zone of rat liver tissue; the nuclear HIFalpha proteins, however, did not appear to be zonated.
- Doerks T, Copley R, Bork P
- DDT -- a novel domain in different transcription and chromosome remodeling factors.
- Trends Biochem Sci. 2001; 26: 145-6
- Display abstract
Homology-based sequence analyses have revealed the presence of a novel domain (DDT) in bromodomain PHD finger transcription factors (BPTFs), chromatin remodeling factors of the BAZ-family and other putative nuclear proteins. This domain is characterized by a number of conserved aromatic and charged residues and is predicted to consist of three alpha helices. Recent studies indicate a likely DNA-binding function for the DDT domain.
- Mount SM, Anderson P
- Expanding the definition of informational suppression.
- Trends Genet. 2000; 16: 157-157
- Coumailleau P et al.
- Characterization and developmental expression of xSim, a Xenopus bHLH/PAS gene related to the Drosophila neurogenic master gene single-minded.
- Mech Dev. 2000; 99: 163-6
- Display abstract
We have isolated a novel gene from Xenopus, denominated xSim, which encodes a protein of 760 amino acids containing a basic helix-loop-helix (bHLH) motif contiguous to a PAS domain characteristic of an emerging family of transcriptional regulators so called bHLH/PAS. xSim shares a strong amino acid sequence identity with the Drosophila Single-minded (dSim) and with the murine Sim1 and Sim2 proteins. Phylogenetic analysis reveals that xSim gene is an ortholog gene of the mSim2 gene. Spatio-temporal analysis shows a maternal and a zygotic expression of xSim throughout early Xenopus development. In situ hybridization assays reveal that the transcripts are enriched in the animal hemisphere until blastula stage and extend to the marginal zone at early gastrula stage. As development proceeds, xSim is mainly restricted to the central nervous system.
- Lechner MS, Levitan I, Dressler GR
- PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin.
- Nucleic Acids Res. 2000; 28: 2741-51
- Display abstract
The Pax gene family encodes transcription factors essential for organ and tissue development in higher eukaryotes. Pax proteins are modular with an N-terminal DNA binding domain, a C-terminal transcription activation domain, and a transcription repression domain called the octapeptide. How these domains interact with the cellular machinery remains unclear. In this report, we describe the isolation and characterization of a novel gene and its encoded protein, PTIP, which binds to the activation domain of Pax2 and other Pax proteins. PTIP binds to Pax2 in vitro, in the yeast two-hybrid assay and in tissue culture cells. The binding of PTIP to Pax2 is inhibited by the octapeptide repression domain. The PTIP protein contains five BRCT domains, first identified in BRCA1 and other nuclear proteins involved in DNA repair/recombination or cell cycle control. Pax2 and PTIP co-localize in the cell nucleus to actively expressed chromatin and the nuclear matrix fraction. For the first time, these results point to a link between Pax transcription factors and active chromatin.
- Arrowsmith CH
- Structure and function in the p53 family.
- Cell Death Differ. 1999; 6: 1169-73
- Display abstract
The recent discovery of several p53 homologs has uncovered a p53 superfamily of transcription factors that can trigger cell cycle arrest and apoptosis. The challenge now is to understand the similarities and differences between family members especially in terms of their regulation and potential for physical or genetic interactions with one another. This review summarizes recent progress in understanding the structure-function relationship within the p53 family. The new family members, p63 and p73, have an additional conserved domain at their C-termini which may have a regulatory function. The structure of this domain (a SAM domain) suggests that it is a protein-protein interaction module that may be involved in developmental processes. The oligomerization domains of p53 family members, while conserved in sequence and three-dimensional structure do not interact appreciably with other family members, but do mediate interactions between the multiple splice variants from an individual gene.
- Caceres C et al.
- DNA-interacting proteins in the spermiogenesis of the mollusc Murex brandaris.
- J Biol Chem. 1999; 274: 649-56
- Display abstract
Sperm chromatin of Murex brandaris (a neogastropod mollusc) undergoes a series of structural transitions during spermiogenesis. The DNA-interacting proteins responsible for these changes as well as the mature protamines present in the ripe sperm nucleus have been characterized. The results reveal that spermiogenic nuclear proteins are protamine precursors that are subjected to a substantial number of small N-terminal deletions that gradually modify their overall charge. The composition of mature protamines is remarkably simple in turn, promoting an efficient and extremely tight packaging of DNA. The pattern of spermiogenic chromatin condensation in M. brandaris clearly departs from that corresponding to vertebrate chromatin.
- Zhu G, Davis TN
- The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole body.
- Biochim Biophys Acta. 1998; 1448: 236-44
- Display abstract
We previously identified HCM1 as a dosage-dependent suppressor of a calmodulin temperature-sensitive mutant (cmd1-1). Calmodulin performs multiple functions in yeast. Here we demonstrate that the effects of HCM1 are specific to the role of calmodulin at the spindle pole body. Overexpression of HCM1 fully suppresses the temperature sensitivity of a calmodulin mutant (cmd1-3) that only has defects in assembly of the spindle pole body but does not suppress the temperature sensitivity of a calmodulin mutant (cmd1-8) that only affects other functions of calmodulin. The DNA binding specificity of Hcm1p was determined by a selection, amplification and binding protocol. The consensus sequence for an Hcmlp binding site is WAAYAAACAAW. Mutations in the DNA binding domain of Hcm1p abolish the ability of Hcmlp to specifically recognize this binding site and abolish the ability of Hcm1p to act as a suppressor of calmodulin mutants. The promoter of SPC110 contains a match to the consensus binding site. Deletion of HCM1 does not affect the basal level of SPC110 transcription, but reduces the induction that occurs late in G1 of the cell cycle.
- Hanson RW
- Biological role of the isoforms of C/EBP minireview series.
- J Biol Chem. 1998; 273: 28543-28543
- Ribar B, Banrevi A, Sipiczki M
- sep1+ encodes a transcription-factor homologue of the HNF-3/forkhead DNA-binding-domain family in Schizosaccharomyces pombe.
- Gene. 1997; 202: 1-5
- Display abstract
We report on the cloning of sep1+, a gene whose mutation causes filamentous growth in Schizosaccharomyces pombe. Since cell growth and propagation are not affected by the mutation, it could not be cloned using selective conditions for the identification of the positive transformants. Instead, we cloned it from a cosmid of a contig (Hoheisel et al., Cell 73, 109-1120, 1993) supposed to cover the chromosomal region where the sep1-1 mutation mapped. The 1761 bp long ORF codes for a protein containing a sequence similar to the DNA-binding domains of the HNF-3/forkhead family of transcription factors.
- Miura N, Iida K, Kakinuma H, Yang XL, Sugiyama T
- Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures.
- Genomics. 1997; 41: 489-92
- Display abstract
The very recently found evolutionarily conserved DNA-binding domain of 100 amino acids, termed the fork head domain, emerged from a sequence comparison of the rat hepatocyte transcription factor HNF-3 alpha and the homeotic gene fork head of Drosophila. We previously isolated a new member of this family, the mesenchyme fork head-1 (MFH-1) gene, which is expressed in developing mesenchyme. Here we describe the isolation of the mouse (MFH-1) and human (FKHL14) chromosomal MFH-1 genes and the determination of the gene and protein structures of MFH-1. We found that the MFH-1 gene has no introns and that the identity of the amino acid sequences of mouse and human MFH-1 proteins is 94%. We also investigated the transcriptional activity of the mouse and human MFH-1 proteins and found that both proteins act as positive transactivators.
- Cullen P
- Genetics and molecular biology.
- Curr Opin Lipidol. 1997; 8: 335-335
- Shimeld SM
- A transcriptional modification motif encoded by homeobox and fork head genes.
- FEBS Lett. 1997; 410: 124-5
- Display abstract
Homeodomain and fork head domain proteins are thought to act as transcription factors by binding to specific DNA target sequences and interacting with other proteins. Here I describe a motif which is present in members of both groups of transcription factor and which has been shown to modulate their ability to activate transcription. The presence of this motif in both homeodomain and fork head proteins indicates they may control transcription by a similar molecular mechanism, perhaps by interacting with the same cofactors.
- Nietfeld W, Meyerhans A
- Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of mouse Ikaros/LyF-1.
- Immunol Lett. 1996; 49: 139-41
- Taniguchi Y, Sasaki Y
- Rapid communication: nucleotide sequence of bovine C/EBP alpha gene.
- J Anim Sci. 1996; 74: 2554-2554
- Avraham KB et al.
- Murine chromosomal location of eight members of the hepatocyte nuclear factor 3/fork head winged helix family of transcription factors.
- Genomics. 1995; 25: 388-93
- Display abstract
A 100-amino-acid DNA-binding motif, known as the winged helix, was first identified in the mammalian hepatocyte nuclear factor-3 (HNF-3) and Drosophila fork head family of transcription factors. Subsequently, more than 40 different genes that contain the winged helix motif have been identified. In the studies described here, we have determined the murine chromosomal location of eight members of this gene family, HFH-1, HFH-3, HFH-4, HFH-5, HFH-6, HFH-8, BF-1, and BF-2, by interspecific backcross analysis. These genes, designated HNF-3 fork head homolog 1 (Hfh1), Hfh3, Hfh4, Hfh5, Hfh6, Hfh8, Hfh9, and Hfh10, respectively, mapped to 6 different mouse autosomes and are thus well dispersed throughout the mouse genome. Based on this mapping information, we predict the chromosomal location of these genes in humans and discuss the potential of these genes as candidates for uncloned mouse mutations.
- Qian X, Costa RH
- Analysis of hepatocyte nuclear factor-3 beta protein domains required for transcriptional activation and nuclear targeting.
- Nucleic Acids Res. 1995; 23: 1184-91
- Display abstract
Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta and gamma) regulate transcription of the transthyretin (TTR) and numerous other liver-specific genes. The HNF-3 proteins bind DNA via a homologous winged helix motif common to a number of developmental regulatory proteins including the Drosophila homeotic fork head (fkh) protein. The mammalian HNF-3/fkh family consists of at least thirty distinct members and is expressed in a variety of different cellular lineages. In addition to the winged helix motif, several HNF-3/fkh family members also share homology within transcriptional activation region II and III sequences. In the present study we further define the sequence boundaries of the HNF-3 beta N-terminal transcriptional activation domain to extend from amino acids 14 to 93 and include conserved region IV and V sequences. We also demonstrate that activity of the HNF-3 N-terminal domain was diminished by mutations which altered a putative alpha-helical structure located between amino acid residues 14 and 19. However, transcriptional activity was not affected by mutations which eliminated two conserved casein kinase I sites or increased the number of acidic amino acid residues in the N-terminal domain. Furthermore, we determined that the nuclear localization signal overlaps with the winged helix DNA-binding motif. These results suggest that conserved sequences within the winged helix motif of the HNF-3/fkh family may be involved not only in DNA recognition, but also in nuclear targeting.
- Swindells MB
- Identification of a common fold in the replication terminator protein suggests a possible mode for DNA binding.
- Trends Biochem Sci. 1995; 20: 300-2
- Dirksen ML, Jamrich M
- Differential expression of fork head genes during early Xenopus and zebrafish development.
- Dev Genet. 1995; 17: 107-16
- Display abstract
Intense efforts have been devoted to the identification of genes that are causatively involved in pattern-forming events of invertebrates and vertebrates. Several gene families involved in this process have been identified. Here we focus on the Xenopus fork head domain gene family. One of its members, XFKH1/Pintallavis/XFD1, has been shown previously to be involved in axial formation, and the expression patterns of the other family members discussed below suggest that they too play a major role in the initial steps of patterning and axial organization. In this report, we describe four Xenopus fork head genes (XFKH3, 4, 5, and 6) and analyze the distribution of their transcripts during early development. XFKH3 is expressed in developing somites but not notochord, XFKH4 in forebrain, anterior retina, and neural crest cells, and XFKH5 in a subset of epidermal cells and the neural floor plate. Finally, transcripts of XFKH6 are seen in neural crest-derived cranial ganglia. In addition, we show that at least some of the zebrafish fork head genes might serve a comparable function. Zebrafish zf-FKH1 has a similar expression pattern as Xenopus XFKH1/Pintallavis/XFD1. It is transcribed in the notochord and neural floor plate. The polster or "pillow" also shows very high levels of zf-FKH1 mRNA.
- Zaret KS, Stevens K
- Expression of a highly unstable and insoluble transcription factor in Escherichia coli: purification and characterization of the fork head homolog HNF3 alpha.
- Protein Expr Purif. 1995; 6: 821-5
- Display abstract
The HNF3 alpha transcription factor is highly enriched in adult hepatocytes and activates many liver-specific genes; its expression in hepatic primordia and neurogenic tissue implies a developmental role. HNF3 alpha is a member of a family of proteins, including fork head in Drosophila, which bind DNA at specific sites using a newly defined "winged helix" structural motif. We describe here the expression and purification of full-length HNF3 alpha containing an amino-terminal histidine tag and show that the protein binds DNA with dissociation constant in the sub-nanomolar range. The techniques used to isolate HNF3 alpha should be applicable to other members of the HNF3/fork head family which appear to be generally unstable and insoluble in Escherichia coli.
- Kaufmann E, Hoch M, Jackle H
- The interaction of DNA with the DNA-binding domain encoded by the Drosophila gene fork head.
- Eur J Biochem. 1994; 223: 329-37
- Display abstract
The Drosophila gene fork head (fkh) encodes a nuclear protein which shares sequence similarity with the rat hepatocyte-enriched transcription factor family HNF3 alpha-gamma. The sequence similarity is restricted to the region that has been defined as the DNA-binding domain of these proteins, termed the fork head domain. In this study, we investigate the structural properties of the fork head domain of the prototype of this protein family encoded by fkh and its interaction with DNA. The core sequence required for DNA binding of the fork head domain consists of 114 amino acids and represents a stable and highly compact monomer of globular structure with an alpha-helix content of 37%. The fork head domain binds specifically to the DNA target sequence of HNF3 alpha-gamma and to an enhancer element that is derived from a regulatory sequence of an in vivo Drosophila target gene. The specific interaction between the DNA-binding domain of the fkh-encoded protein and its target DNA is mediated by two contact regions which are separated from each other by one turn of the DNA. Our data are consistent with a structural model which derived rom X-ray diffraction analysis of the DNA-binding domain of HNF3 gamma. Differences concerning the DNA contact sites between the DNA-binding domain of the fkh-encoded protein and the HNF3 protein family are discussed.
- Pierrou S, Hellqvist M, Samuelsson L, Enerback S, Carlsson P
- Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.
- EMBO J. 1994; 13: 5002-12
- Display abstract
The forkhead domain is a monomeric DNA binding motif that defines a rapidly growing family of eukaryotic transcriptional regulators. Genetic and biochemical data suggest a central role in embryonic development for genes encoding forkhead proteins. We have used PCR and low stringency hybridization to isolate clones from human cDNA and genomic libraries that represent seven novel forkhead genes, freac-1 to freac-7. The spatial patterns of expression for the seven freac genes range from specific for a single tissue to nearly ubiquitous. The DNA binding specificities of four of the FREAC proteins were determined by selection of binding sites from random sequence oligonucleotides. The binding sites for all four FREAC proteins share a core sequence, RTAAAYA, but differ in the positions flanking the core. Domain swaps between two FREAC proteins identified two subregions within the forkhead domain as responsible for creating differences in DNA binding specificity. Applying a circular permutation assay, we show that binding of FREAC proteins to their cognate sites results in bending of the DNA at an angle of 80-90 degrees.
- Fogolari F, Esposito G, Viglino P, Damante G, Pastore A
- Homology model building of the thyroid transcription factor 1 homeodomain.
- Protein Eng. 1993; 6: 513-9
- Display abstract
A possible structure for the homeodomain of rat thyroid transcription factor 1 is proposed on the basis of the homology with other homeodomains whose structures have been solved by X-ray crystallography. A structure very similar to the reference ones is feasible and may account for the observed DNA-binding specificity. Structural features of the model, which are likely to be shared by other homeodomains, are discussed and may help researchers in the field to analyse their own experimental data.
- Clevidence DE et al.
- Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family.
- Proc Natl Acad Sci U S A. 1993; 90: 3948-52
- Display abstract
Hepatocyte nuclear factor (HNF)-3 alpha, -3 beta, and -3 gamma are liver transcription factors that mediate the coordinate expression of a number of hepatocyte-specific genes. The HNF-3 proteins share DNA-binding-domain homology among themselves and with the Drosophila homeotic protein forkhead (fkh). The HNF-3/fkh DNA-binding domain constitutes an uncharacterized protein motif that recognizes its cognate DNA binding site as a monomer. Additional HNF-3/fkh-related proteins are known to be required for determination events during embryogenesis in Drosophila and Xenopus. In this report, we describe the isolation of nine additional HNF-3/fkh homologue (HFH) clones from rodent tissue cDNAs by using both low-stringency hybridization and a polymerase chain reaction protocol. Many of the HFH genes exhibit a tissue-restricted expression pattern and are transcribed in tissues other than liver, including brain, kidney, lung, and intestine. The HNF-3/fkh motif therefore comprises a large gene family of transcription factors that play a role in tissue-specific gene regulation and development.
- Li C, Tucker PW
- DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain.
- Proc Natl Acad Sci U S A. 1993; 90: 11583-7
- Display abstract
An 84-amino acid segment of QRF-1 [glutamine (Q)-rich factor 1], a newly cloned, B-cell-derived DNA-binding protein, shows significant sequence homology with the DNA-binding domains of the hepatocyte nuclear factor 3/fork head family of proteins. Here we demonstrate that this 84-amino acid domain is necessary and sufficient for DNA binding. We also propose a secondary structural model for the domain. At the N-terminal portion of the model, a basic hook structure is followed by two amphipathic helices separated by a turn. Invariant amino acid residues within the two proposed helices form the hydrophobic cores. An aromatic kink and a third amphipathic helix comprise the center of the domain. At the C terminus, two variable-length loops flank a putative 7-amino acid helix followed by a short basic region.
- Landsman D
- No HMG-1 box signature.
- Nature. 1993; 363: 590-590
- Ruiz i Altaba A, Prezioso VR, Darnell JE, Jessell TM
- Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate.
- Mech Dev. 1993; 44: 91-108
- Display abstract
Axial patterning in the nervous system of vertebrate embryos depends on inductive signals that derive from the organizer region (the dorsal lip in amphibians and the node in birds and mammals) and leter from the notochord and floor plate. Previous studies have shown that Pintallavis, a member of the HNF-3/fork head transcription factor family, is expressed selectively by these cell groups in frog embryos and may be involved in regulating neural development. We report here that in early rat and mouse embryos, the embryonic endoderm, the node, the notochord and the floor plate express two related transcription factors, HNF-3 alpha and HNF-3 beta, which also function in the control of liver cell differentiation. Early embryonic tissues express variant forms of HNF-3 beta which derive from the use of 5' alternative exons. Within the organizer region and notochord, HNF-3 beta and HNF-3 alpha have distinct temporal patterns of expression and appear in partially overlapping domains. The early expression pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate cells is similar to that of Pintallavis in frog embryos. There does not appear to be a Pintallavis homologue in mice. This prompted us to isolate and analyze the expression of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expressed in the dorsal lip, pharyngeal endoderm and floor plate. In contrast to mammalian HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after neural tube closure. Thus, the combined expression patterns of Pintallavis and HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within neural tissue, the onset of expression of these regulatory genes define successive stages in the differentiation of floor plate cells. The results reported here show that closely related members of the HNF-3/fork head gene family are expressed by axial midline cell groups involved in neural induction and patterning and suggest the involvement of these genes in the development of the vertebrate neuraxis.
- Emerson CP Jr
- Skeletal myogenesis: genetics and embryology to the fore.
- Curr Opin Genet Dev. 1993; 3: 265-74
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The MyoD family of transcription factors are expressed in the skeletal muscles of vertebrate and invertebrate embryos and have dominant regulatory activities that indicate their important developmental functions in myogenic lineage determination and muscle differentiation. Genetic studies, however, reveal that individually, myoD-related genes are not essential for myogenic lineage determination in mouse and Caenorhabditis elegans embryos, but have differentiation functions and perhaps redundant functions in lineage determination that remain to be defined by further genetic studies.
- Lai E, Clark KL, Burley SK, Darnell JE Jr
- Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function.
- Proc Natl Acad Sci U S A. 1993; 90: 10421-3
- Display abstract
A family of transcription factors, first identified as hepatocyte nuclear factors (HNF-3 alpha, -3 beta, and -3 gamma) and as a homeotic Drosophila mutant, fork head, has been intensively studied for the past 4 years. Important findings have emerged about the structure of the DNA-binding portion of the proteins as well as biologic discoveries about the diversity of the family and its implied role in early development.
- Miura N, Wanaka A, Tohyama M, Tanaka K
- MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme.
- FEBS Lett. 1993; 326: 171-6
- Display abstract
We have isolated a novel mouse gene, MFH-1 (mesenchyme fork head 1) that is related to the Drosophila fork head and rat HNF3 genes. MFH-1 encodes a distinct fork head domain that is classified into a distinct subfamily. A recombinant MFH-1 protein could bind to the HNF3 binding site. MFH-1 is expressed temporally in developing embryos, first in the non-notochordal mesoderm and later in areas of mesenchymal condensation in the trunk, head, and limbs. Our results suggest that MFH-1 might be involved in the formation of special mesenchymal tissues.
- Brennan RG
- The winged-helix DNA-binding motif: another helix-turn-helix takeoff.
- Cell. 1993; 74: 773-6
- Pani L, Overdier DG, Porcella A, Qian X, Lai E, Costa RH
- Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein.
- Mol Cell Biol. 1992; 12: 3723-32
- Display abstract
The hepatocyte nuclear factor 3 (HNF-3) gene family is composed of three proteins (alpha, beta, and gamma) that are transcription factors involved in the coordinate expression of several liver genes. All three proteins share strong homology in their DNA binding domains (region I) and are able to recognize the same DNA sequence. They also possess two similar stretches of amino acids at the carboxyl terminus (regions II and III) and a fourth segment of homology at the amino terminus (region IV). Furthermore, the HNF-3 proteins demonstrate homology with the Drosophila homeotic gene fork head in regions I, II, and III, suggesting that HNF-3 may be its mammalian homolog. In order to define HNF-3 beta protein domains involved in transcriptional activation, we have used a reporter gene, whose transcription is dependent on HNF-3 binding, for hepatoma cell cotransfection assays with expression vectors that produced different truncated HNF-3 beta proteins. A position-independent activation domain which contained conserved regions II and III was identified at the carboxyl terminus of the HNF-3 beta protein (amino acids 361 to 458). Moreover, site-directed mutations that altered the sequences within regions II and III demonstrated their importance to transactivation. The region II-III domain does not possess amino acid sequences in common with other transcription factors and may define a novel activation motif. HNF-3 beta amino-terminal sequences defined by conserved region IV also contributed to transactivation, but region IV activity required the participation of the region II-III domain. Region IV is abundant in serine amino acids and contains two putative casein kinase I phosphorylation sites, a feature similar to protein motifs described for the transcription factors Pit-1/GHF-1 and HNF-1.
- Tao W, Lai E
- Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain.
- Neuron. 1992; 8: 957-66
- Display abstract
We have previously characterized a novel transcription factor family in mammals, the HNF-3 family, by the members' homology to one another and to the Drosophila homeotic gene fork head. The expression of fork head is restricted to the anterior and posterior termini of the early fly embryo. Brain factor 1 (BF-1) is a new member of this family isolated from rat brain with an expression pattern and DNA binding specificity distinct from the HNF-3 genes. Expression is highly restricted in the developing neural tube to its rostral end, which gives rise to the telencephalon. These results suggest that BF-1 plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
- Hacker U, Grossniklaus U, Gehring WJ, Jackle H
- Developmentally regulated Drosophila gene family encoding the fork head domain.
- Proc Natl Acad Sci U S A. 1992; 89: 8754-8
- Display abstract
We have isolated seven Drosophila genes by means of low-stringency hybridization to a DNA probe containing the coding sequence for the protein domain shared by the rodent hepatocyte-enriched nuclear transcription factor HNF3A (alpha) and the product of the Drosophila region-specific homeotic gene fork head (fkh). The previously unreported genes encode a 110-amino acid conserved sequence, which we call the fork head (fkh) domain. Two of these fkh-domain-encoding genes ("FD genes") map to the sloppy paired locus (slp), which exerts segmentation gene function. The expression patterns of the other FD genes suggest that their protein products are likely to be involved in gut formation, mesoderm specification, and some specific aspects of neural development. The FD gene products presumably represent a family of transcription factors that, like the previously identified DNA-binding proteins, contribute to early developmental decisions in cell fates during embryogenesis.
- Treisman R, Ammerer G
- The SRF and MCM1 transcription factors.
- Curr Opin Genet Dev. 1992; 2: 221-6
- Display abstract
The mammalian transcription factor SRF (serum-response factor) and the related Saccharomyces cerevisiae transcription factor MCM1 are the prototypes of a new class of dimeric DNA-binding proteins. Their function is regulated in part by the interactions of their DNA-binding domains with accessory proteins. Recent work has advanced the functional characterization of the contributions of SRF and MCM1, and their accessory proteins to transcriptional activation.
- LaMarco K, Thompson CC, Byers BP, Walton EM, McKnight SL
- Identification of Ets- and notch-related subunits in GA binding protein.
- Science. 1991; 253: 789-92
- Display abstract
Recombinant cDNA clones that encode two distinct subunits of the transcription factor GA binding protein (GABP) have been isolated. The predicted amino acid sequence of one subunit, GABP alpha, exhibits similarity to the sequence of the product of the ets-1 protooncogene in a region known to encompass the Ets DNA binding domain. The sequence of the second subunit, GABP beta, contains four 33-amino acid repeats located close to the NH2-terminus of the subunit. The sequences of these repeats are similar to repeats in several transmembrane proteins, including Notch from Drosophila melanogaster and Glp-1 and Lin-12 from Caenorhabditis elegans. Avid, sequence-specific binding to DNA required the presence of both polypeptides, revealing a conceptual convergence of nuclear transforming proteins and membrane-anchored proteins implicated in developmentally regulated signal transduction processes.
- Lai E, Prezioso VR, Tao WF, Chen WS, Darnell JE Jr
- Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head.
- Genes Dev. 1991; 5: 416-27
- Display abstract
By analysis of cDNA clones that cross-hybridized with a portion of the cDNA encoding the recently described rat protein hepatocyte nuclear factor 3 alpha (HNF-3 alpha, previously called HNF-3A), we now describe two additional members, HNF-3 beta and HNF-3 gamma, of this gene family. A 110-amino-acid region in the DNA-binding domain of this family is not only very highly conserved in rodents (HNF-3 alpha, -3 beta, and -3 gamma are identical in 93 of 110 amino acids in this region) but also in Drosophila where the homeotic gene fork head has 88 of the 93 residues that are identical in the three rat genes. The HNF-3 family in rodents is expressed in cells that derive from the lining of the primitive gut; some of the embryonic Drosophila cells in which fork head is expressed also give rise to gut and salivary glands. Thus, it appears that this gene family, the DNA-binding portion of which is unlike that of any previously recognized DNA-binding proteins, may contribute to differentiation of cells in internal organs in both vertebrates and invertebrates.
- Damante G, Di Lauro R
- Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity.
- Proc Natl Acad Sci U S A. 1991; 88: 5388-92
- Display abstract
The DNA binding specificities of the homeodomains contained in thyroid transcription factor 1 and Antennapedia have been compared. The two homeodomains recognize different DNA sequences, despite the similar amino acid sequences of their recognition helix. Mutations that make the recognition helix of thyroid transcription factor 1 identical to the one contained in Antennapedia have no effects on the binding specificity of thyroid transcription factor 1. The exchange of other segments between these two homeodomains allows the identification of the regions responsible for the observed DNA binding specificities. These results indicate that amino acid residues outside of the recognition helix play an important role in the determination of the DNA binding specificities of these two homeodomains.
- Lai E, Darnell JE Jr
- Transcriptional control in hepatocytes: a window on development.
- Trends Biochem Sci. 1991; 16: 427-30
- Display abstract
The unique phenotype of each differentiated cell in an animal (or plant) arises from selective expression of genes in a cell- or tissue-specific fashion, which is controlled primarily at the level of transcription. This review will focus on transcription factors that regulate cell-specific transcription in one intensely studied cell type, the hepatocyte or parenchymal liver cell. All of the recently isolated transcription factors that are important in hepatocyte-specific gene expression were identified in adult liver and there are strong hints that some of these may play an important role in embryogenesis.
