NORMAL GENOMIC

• Schwartz HT, Horvitz HR
• The C. elegans protein CEH-30 protects male-specific neurons fromapoptosis independently of the Bcl-2 homolog CED-9.
• Genes Dev. 2007; 21: 3181-94
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• The developmental control of apoptosis is fundamental and important. Wereport that the Caenorhabditis elegans Bar homeodomain transcriptionfactor CEH-30 is required for the sexually dimorphic survival of themale-specific CEM (cephalic male) sensory neurons; the homologous cells ofhermaphrodites undergo programmed cell death. We propose that thecell-type-specific anti-apoptotic gene ceh-30 is transcriptionallyrepressed by the TRA-1 transcription factor, the terminal regulator ofsexual identity in C. elegans, to cause hermaphrodite-specific CEM death.The established mechanism for the regulation of specific programmed celldeaths in C. elegans is the transcriptional control of the BH3-only geneegl-1, which inhibits the Bcl-2 homolog ced-9; similarly, most regulationof vertebrate apoptosis involves the Bcl-2 superfamily. In contrast,ceh-30 acts within the CEM neurons to promote their survival independentlyof both egl-1 and ced-9. Mammalian ceh-30 homologs can substitute forceh-30 in C. elegans. Mice lacking the ceh-30 homolog Barhl1 show aprogressive loss of sensory neurons and increased sensory-neuron celldeath. Based on these observations, we suggest that the function of Barhomeodomain proteins as cell-type-specific inhibitors of apoptosis isevolutionarily conserved.

• Cahill A
• A tale of a few hospitals.
• Aust Health Rev. 2004; 27: 1-4

• Ding Z, Gillespie LL, Paterno GD
• Human MI-ER1 alpha and beta function as transcriptional repressors byrecruitment of histone deacetylase 1 to their conserved ELM2 domain.
• Mol Cell Biol. 2003; 23: 250-8
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• mi-er1 (previously called er1) was first isolated from Xenopus laevisembryonic cells as a novel fibroblast growth factor-regulatedimmediate-early gene. Xmi-er1 was shown to encode a nuclear protein withan N-terminal acidic transcription activation domain. The human orthologueof mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at theamino acid level and was shown to be upregulated in breast carcinoma celllines and tumors. Alternative splicing at the 3' end of hmi-er1 producestwo major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinctC-terminal domains. In this study, we investigated the role ofhMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Usingfusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNAbinding domain, we show that both isoforms, when recruited to the G5tkCATminimal promoter, function to repress transcription. We demonstrate thatthis repressor activity is due to interaction and recruitment of atrichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore,deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha andhMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain wasfirst described in the Caenorhabditis elegans Egl-27 protein and ispresent in a number of SANT domain-containing transcription factors. Thisis the first report of a function for the ELM2 domain, highlighting itsrole in the regulation of transcription.

• Lanjuin A, VanHoven MK, Bargmann CI, Thompson JK, Sengupta P
• Otx/otd homeobox genes specify distinct sensory neuron identities in C.elegans.
• Dev Cell. 2003; 5: 621-33
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• The mechanisms by which the diverse functional identities of neurons aregenerated are poorly understood. C. elegans responds to thermal andchemical stimuli using 12 types of sensory neurons. The Otx/otd homologttx-1 specifies the identities of the AFD thermosensory neurons. We showhere that ceh-36 and ceh-37, the remaining two Otx-like genes in the C.elegans genome, specify the identities of AWC, ASE, and AWB chemosensoryneurons, defining a role for this gene family in sensory neuronspecification. All C. elegans Otx genes and rat Otx1 can substitute forceh-37 and ceh-36, but only ceh-37 functionally substitutes for ttx-1.Functional substitution in the AWB neurons is mediated by activation ofthe same downstream target lim-4 by different Otx genes. Misexpressionexperiments indicate that although the specific identity adopted uponexpression of an Otx gene may be constrained by the cellular context,individual Otx genes preferentially promote distinct neuronal identities.

• Biemar F, Devos N, Martial JA, Driever W, Peers B
• Cloning and expression of the TALE superclass homeobox Meis2 gene duringzebrafish embryonic development.
• Mech Dev. 2001; 109: 427-31
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• Meis and Prep/Pknox (MEINOX family) proteins, together with Pbx (PBCfamily) proteins, belong to the TALE superfamily characterized by anatypical homeodomain containing three additional amino acids between helix1 and helix 2. Members of the MEINOX and PBC families have been isolatedin Caenorhabditis elegans, Drosophila, Xenopus, chick, mouse and human,and play crucial roles in many aspects of embryogenesis. Here, we reportthe isolation of meis2 in zebrafish. Expression of meis2 is first detectedat the beginning of gastrulation. Later during embryogenesis, meis2transcripts are found in distinct domains of the central nervous systemwith the strongest expression in the hindbrain. Expression was alsodetected in the isthmus, along the spinal cord and in the lateralmesoderm. As development proceeds, meis2 is also expressed in thedeveloping retina, pharyngeal arches, and in the vicinity of the gut tube.

• Ferrier DE, Brooke NM, Panopoulou G, Holland PW
• The Mnx homeobox gene class defined by HB9, MNR2 and amphioxus AmphiMnx.
• Dev Genes Evol. 2001; 211: 103-7
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• The HB9 homeobox gene has been cloned from several vertebrates and isimplicated in motor neuron differentiation. In the chick, a related gene,MNR2, acts upstream of HB9 in this process. Here we report an amphioxushomologue of these genes and show that it diverged before the geneduplication yielding HB9 and MNR2. AmphiMnx RNA is detected in twoirregular punctate stripes along the developing neural tube, comparable tothe distribution of 'dorsal compartment' motor neurons, and also in dorsalendoderm and posterior mesoderm. We propose a new homeobox class, Mnx, toinclude AmphiMnx, HB9, MNR2 and their Drosophila and echinodermorthologues; we suggest that vertebrate HB9 is renamed Mnx1 and MNR2 berenamed Mnx2.

• Burglin TR
• The PBC domain contains a MEINOX domain: coevolution of Hox and TALEhomeobox genes?
• Dev Genes Evol. 1998; 208: 113-6
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• A recent survey of TALE superclass homeobox genes revealed a new domainupstream of the homeodomain that is conserved between the plant KNOX genesand the animal MEIS genes. At the same time, another paper identified theDrosophila gene homothorax (hth) as a homologue of the vertebrate MEISgenes, which prompted a reexamination of the sequences of the MEIS, KNOX(collectively named MEINOX) and PBC domains. Similarity of the completeMEINOX domain was found within the PBC domain. This suggests that the PBCclass genes were also derived from the ancient MEINOX genes. Recently, ithas been shown that the MEIS genes can interact with the Abd-B genes,whilst previous results have shown that the PBC genes interact withanterior Hox genes. This leads to the hypothesis that the duplication ofan ancestral MEINOX gene into the PBC and MEIS genes happened at a pointin time when the first two Hox cluster genes, an anterior one and aposterior one, emerged, and that subsequently these gene classescoevolved.

• Semina EV, Reiter RS, Murray JC
• A new human homeobox gene OGI2X is a member of the most conserved homeoboxgene family and is expressed during heart development in mouse.
• Hum Mol Genet. 1998; 7: 415-22
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• Homeodomain (HD) proteins are transcription regulators controlling avariety of cell fates. The HD region characterizing this protein family isa domain of 60 amino acid residues that recognizes and binds a site in theregulatory region of the target gene. It has been suggested that regionsoutside the HD may determine the specific functions of the various HDproteins by forming additional contacts with DNA sequences or byinteractions with other proteins. We have identified a 14 amino acid motifwithin the C-terminal region of the protein encoded by the RIEG1 gene thatis conserved among several HD proteins. Overlapping expression of thegenes encoding these proteins during craniofacial development suggestedthat they might interact with a common factor. In order to identifyadditional genes possessing this motif we screened a human craniofacialcDNA library with oligoprobes. A novel gene was identified, exhibiting themost homology to murine Og12x (formerly OG12) and the recently reportedhuman SHOX gene. Human OG12X and murine Og12x are highly homologous andthe OG12X and Og12x proteins are 100% identical. In situ hybridization onmouse embryos ranging from 9 to 16 days post-coitum localized murine Og12xmRNA in the heart, otic region, maxillary and mandibular components of thefirst branchial arch, nasal processes, eyelid, midbrain, medullaoblongata, limbs, dorsal root ganglia and genital tubercle. OG12X wasmapped to human chromosome 3q22-26 and murine Og12x to the syntenic regionon mouse chromosome 3. Based upon the expression pattern of its mousecognate, OG12X represents a candidate for the blepharophimosis (BPES) andCornelia de Lange syndromes previously mapped to this region.

• Yamashita T, Moriyama K, Sheng HZ, Westphal H
• Lhx4, a LIM homeobox gene.
• Genomics. 1997; 44: 144-6
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• LIM homeobox genes are well conserved in evolution and play importantroles as transcriptional regulators of embryonic development. Here wereport on the structure of LIM domains of the mouse Lhx4 (Gsh4) gene. ThecDNA was generated by modified reverse transcription-PCR from midgestationembryo templates, using a degenerate consensus primer. The deduced aminoacid sequence of the first LIM domain reveals 77% identity and that of thesecond domain reveals 86% identity with the corresponding sequences of theclosely related Lhx3 gene. In addition, there is 38-56% similarity toother members of the Lhx gene family. The LIM consensus sequence is wellconserved in Lhx4.