POU Domain Proteins

Abstract Homeodomain transcription factors play essential roles in controlling embryonic development in all animal species studied. Within the super family of homeodomain factors is the POU domain family, which was established on the basis of amino acid sequence homology between the transcription factors ;EITl/GHFl, OCTl, OCT2, and !JNC86 (hence the acronym POU, which is pronounced “pow”) (Herr et al., 1988). PITl/ GHF (Bodner et al., 1988; Ingraham et al., 1988) controls transcription of the growth hormone and other pituitary-specific genes, OCTl (Sturm et al., 1988) is ubiquitously expressed and activates transcription of histone H2B genes, OCT2 (Clerc et al., 1988; Ko et al., 1988) activates transcrip tion of immunoglobulin genes in B lymphocytes, and UNC86 (Finney et al., 1988) determines neuroblast fate in C.elegans. Subsequently, over two dozen POU domain-containing proteins have been identified in C. elegans, Drosophila, and mammals (Verrijzer and Van der Vliet, 1993). A new system of genetic nomenclature has been devised so that the PITl/ GHFl, OCTl, OCT2, and BRN4/OCT9 proteins are encoded by POU1F1, POU2F1, POU2F2, and POU3F4, respectively (reviewed by Ezzell, 1996). The defining characteristic of POU proteins is a bipartite DNA binding domain of 150 to 160 amino acids that consists of a 60-amino acid POU homeodomain (POUH0) located just carboxyl-terminal to a POU-specific domain (POU5) of 70 to 80 amino acids (Fig. 11.1). As described in Chapter 9, the homeodomain contains three a-helical regions so that helices 2 and 3 form a helix-turn-helix motif that is structurally similar to the DNA-binding domain of prokaryotic repressors, in which helix 3 contacts DNA in the major groove (Harrison and Aggar wal, 1990). The POU5 domain contains four a-helical regions so that hel ices 2 and 3 form a helix-turn-helix motif that is similar in its structure to the phage A repressor DNA-binding domain (Assa-Munt et al., 1993).