NORMAL GENOMIC

• Davies B, Schwarz-Sommer Z
• Control of floral organ identity by homeotic MADS-box transcription factors.
• Results Probl Cell Differ. 1994; 20: 235-58

• Ring CJ, Latchman DS
• The human Brn-3b POU transcription factor shows only limited homology to the Brn-3a/RDC-1 factor outside the conserved POU domain.
• Nucleic Acids Res. 1993; 21: 2946-2946

• Goldsborough AS et al.
• Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11.
• Nucleic Acids Res. 1993; 21: 127-34
• Display abstract

• POU domain genes encode a family of highly conserved transacting factors that influence the transcriptional activity of several cell type-specific and ubiquitous genes. We have cloned and sequenced cDNAs encoding a novel mouse POU domain protein, Oct-11, that is closely related within the POU domain to the POU class II proteins, Oct-1 and Oct-2. Recombinant Oct-11 protein binds specifically to an octamer sequence in vitro. The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis. In addition, it is abundant in the myeloma cell line P3/NS-1/1-Ag4.1. We describe the structure of Oct-11 and its chromosomal localization, and discuss the evidence that the POU class II gene family has evolved by duplication and divergence of a common ancestral gene.

• Verrijzer CP, Alkema MJ, van Weperen WW, Van Leeuwen HC, Strating MJ, van der Vliet PC
• The DNA binding specificity of the bipartite POU domain and its subdomains.
• EMBO J. 1992; 11: 4993-5003
• Display abstract

• The POU domain is a conserved DNA binding region of approximately 160 amino acids present in a family of eukaryotic transcription factors that play regulatory roles in development. The POU domain consists of two subdomains, the POU-specific (POUS) domain and a POU-type homeodomain (POUHD). We show here that, like the POUHD, the Oct-1 POUS domain can bind autonomously to DNA but with low affinity. DNA binding studies and in vitro binding site selection revealed that the POU subdomains each have a different sequence specificity. The binding consensus of the POUS domain [gAATAT(G/T)CA] and POUHD (RTAATNA) respectively overlap the 'left half' and right half' of the POU domain recognition sequence [a(a/t)TATGC(A/T) AAT(t/a)t]. In addition to the core sequence, which is very similar to the octamer motif (ATGCAAAT), the flanking bases make a significant contribution to the binding affinity of the POU domain. Interestingly, at some positions the sequence preferences of the isolated POU subdomains are distinct from those of the POU domain, suggesting that the POU domain binding site is more than a simple juxtaposition of the POUS and POUHD target sequences. In addition, analysis of the binding kinetics of the POU domain and POUHD indicates that the POUS domain enhances the binding affinity by reducing the dissociation rate. Our results show that the POU domain proteins have DNA binding properties distinct from those of classic homeodomain proteins. We suggest a model for the way in which an additional conserved domain adds further specificity to DNA recognition by homeodomain proteins.

• De Simone V, Cortese R
• Transcription factors and liver-specific genes.
• Biochim Biophys Acta. 1992; 1132: 119-26

• Lobe CG
• Transcription factors and mammalian development.
• Curr Top Dev Biol. 1992; 27: 351-83

• Faisst S, Meyer S
• Compilation of vertebrate-encoded transcription factors.
• Nucleic Acids Res. 1992; 20: 3-26

• Lazzaro D, De Simone V, De Magistris L, Lehtonen E, Cortese R
• LFB1 and LFB3 homeoproteins are sequentially expressed during kidney development.
• Development. 1992; 114: 469-79
• Display abstract

• LFB1 (HNF-1/HNF-1 alpha/APF) and LFB3 (vHNF-1/HNF-1 beta) are two homeoproteins involved in the transcriptional regulation of several liver-specific genes. Both genes are expressed in the polarized epithelia of a wide range of tissues, including liver, the digestive tract and kidney. We have analyzed the expression pattern of LFB1 and LFB3 in the developing rat kidney by in situ hybridization. Our results show that LFB3 transcripts can be detected in mesoderm-derived cells as soon as they are induced to differentiate into a polarized epithelium, while LFB1 transcripts appear only at a later stage when the three different segments of the nephron become apparent. LFB1 transcripts are restricted to the proximal and distal tubules, whereas LFB3 is also detected in the collecting ducts. Neither LFB1 nor LFB3 are expressed in the glomeruli or in the transition epithelia of the ureters and of the urinary bladder, none of which are involved in active transport mechanisms. The sequential activation of these two genes is also observed in transfilter organ cultures of nephrogenic mesenchyme at different stages after induction. This expression pattern suggests that LFB3 and LFB1 play a role in two critical stages of the developmentally regulated conversion of the nephric mesenchyme into a polarized epithelium: the early inductory phase (LFB3) and the postinductory phase (LFB1+LFB3).

• Frankel AD
• The importance of being flexible.
• Proc Natl Acad Sci U S A. 1992; 89: 11653-11653

• Verrijzer CP, van Oosterhout JA, van Weperen WW, van der Vliet PC
• POU proteins bend DNA via the POU-specific domain.
• EMBO J. 1991; 10: 3007-14
• Display abstract

• POU proteins constitute a family of ubiquitous as well as cell type-specific transcription factors that share the conserved POU DNA binding domain. This domain consists of two distinct subdomains, a POU-specific domain and a POU homeodomain, that are both required for high affinity sequence-specific DNA binding. In a circular permutation assay, several POU proteins, including Oct-1, Oct-2A, Oct-6 and Pit-1, demonstrated a position dependent mobility of the protein-DNA complexes, suggesting induction of DNA bending. This was confirmed by detection of relative bend direction, using pre-bent DNA, and by enhanced ligase mediated cyclization. Bending was caused by interaction with the POU domain. By contrast, binding of the POU homeodomain did not distort the DNA structure, indicating that the POU-specific domain confers DNA bending.

• Wingender E
• Transcription regulating proteins and their recognition sequences.
• Crit Rev Eukaryot Gene Expr. 1990; 1: 11-48

• Benditt J
• POU! Goes the homeobox.
• Sci Am. 1989; 260: 2022-2022

• Castrillo JL, Bodner M, Karin M
• Purification of growth hormone-specific transcription factor GHF-1 containing homeobox.
• Science. 1989; 243: 814-7
• Display abstract

• Pituitary-specific expression of the growth hormone (GH) gene is governed by a transcription factor, GHF-1, that binds to two sites within its promoter. Recently, GHF-1 was shown to be a member of the homeobox family of DNA-binding proteins. An important question is whether GHF-1 controls the expression of other pituitary specific genes, such as prolactin (Prl), expressed in closely related cell types. To this end, GHF-1 was purified from extracts of GH- and Prl-expressing pituitary tumor cells and identified as a 33-kilodalton polypeptide. Although GHF-1 bound to and activated the GH promoter, it did not recognize the Prl promoter. However, at least one other factor in the same extracts, which was easily separated from GHF-1, bound to several sites within the Prl but not the GH promoter. Antibodies to GHF-1 did not react with the Prl binding activity. These results imply that the pituitary-specific expression of GH and Prl is governed by two distinct trans-acting factors.

• Short NJ
• Regulation of transcription. Flexible interpretation.
• Nature. 1988; 334: 192-3

• Snow MH
• New data from mammalian homoeobox-containing genes.
• Nature. 1986; 324: 618-9

• Travers A
• Sigma factors in multitude.
• Nature. 1985; 313: 15-6