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POU Domain Family Values: Flexibility, Partnerships, and Developmental Codes

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POU Domain Family Values: Flexibility, Partnerships, and Developmental Codes Downloaded from genesdev.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW POU domain family values: flexibility, partnerships, and developmental codes Aimee K. Ryan and Michael G. Rosenfeld 1 Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, Califiornia 92093-0648 USA Transcription factors serve critical roles in the progres- primary focus of this review. Crystallization of the Oct-1 sive development of general body plan, organ commit- and Pit-1 POU domains on DNA and in vitro studies ment, and finally, specific cell types. It has been the hope examining the specificity of POU domain cofactor inter- of most developmental biologists that comparison of the actions suggest that the flexibility with which the POU biological roles of a series of individual members within domain recognizes DNA-binding sites is a critical com- a family will permit at least some predictive generaliza- ponent of its ability to regulate gene expression. The tions regarding the developmental events that are likely implications of these data with respect to the mecha- to be regulated by a particular class of transcription fac- nisms utilized by the POU domain family of transcrip- tors. Here, we present an overview of the developmental tion factors to control developmental events will also be functions of the family of transcription factors charac- discussed. terized by the POU DNA-binding motif afforded by re- cent in vivo studies. Conformation of the POU domain on DNA The POU domain family of transcription factors was defined following the observation that the products of High-affinity site-specific DNA binding by POU domain three mammalian genes, Pit-l, Oct-l, and Oct-2 and the transcription factors requires both the POU-specific do- protein encoded by the Caenorhabditis elegans gene main and the POU homeodomain (Sturm and Herr 1988; unc-86 shared a region of homology, known as the POU Ingraham et al. 1990; Kristie and Sharp 1990; Verrijzer et domain (Bodner et al. 1988; Clerc et al. 1988; Finney et al. 1990, 1992). The two subdomains can cooperatively al. 1988; Herr et al. 1988; Ingraham et al. 1988; Ko et al. bind DNA even when they are not joined by the linker 1988; MUller et al. 1988; Scheidereit et al. 1988; Sturm et (Klemm and Pabo 1996). Resolution of the crystal struc- al. 1988). The POU domain is a bipartite DNA-binding tures of Oct-1 and Pit-1 POU domains bound to DNA as domain (Sturm and Herr 1988; Ingraham et al. 1990; Bot- a monomer and homodimer, respectively, confirmed field et al. 1992; Verrijzer et al. 1992), consisting of two several of the in vitro findings regarding interactions of highly conserved regions tethered by a variable linker. this bipartite DNA-binding domain with DNA and has The -75-amino acid amino-terminal region was called provided important information regarding the flexibility the POU-specific domain and the carboxy-terminal 60- and versatility of POU domain proteins (Klemm et al. amino acid region, the POU homeodomain. 1994; Jacobson et al. 1997). POU domain proteins have been identified from a di- verse range of species (Table 1). Although currently Structure of Oct-1 bound to an octamer DNA-binding grouped into six or seven classes based on the amino acid site sequence of their POU domains and conservation of the variable linker region (Wegner et al. 1993a), the recent Overall the crystal structure of a monomer of the Oct-1 identification and characterization of several new POU POU domain bound to the octamer element was similar domain proteins suggests that some classes may be fur- to that predicted by the nuclear magnetic resonance ther subdivided (Spaniol et al. 1996). The in vivo func- (NMR) solution structures of the POU-specific domain tions of many POU proteins have been examined (Assa-Munt et al. 1993; Dekker et al. 1993) and the POU through targeted gene disruption in the mouse and char- homeodomain (Sivaraja et al. 1994; Cox et al. 1995; acterization of loss-of-function and gain-of-function mu- Morita et al. 1995) in isolation. The POU-specific do- tations in Drosophila, C. elegans, and Xenopus. These in main consists of four ~ helices, with the second and third vivo studies demonstrate that POU domain proteins helices forming a structure similar to the helix-turn- regulate key developmental processes and will be the helix motif of the K and 434 repressors; several of the DNA base contacts are also conserved (Klemm et al. 1994). Although the primary sequence of the Oct-1 POU ~Corresponding author. homeodomain is considerably divergent from those of E-MAIL [email protected]; FAX (619) 534-8180. classic homeodomains, it is structurally conserved and GENES & DEVELOPMENT 11:1207-1225 © 1997 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/97 $5.00 1207 Downloaded from genesdev.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Ryan and Rosenfeld Table 1. Summary of expression patterns and biological functions of POU domain proteins Class Factora Expression pattern Function I Pit-1 [M] anterior pituitary gland-- determination of somatotrope, somatotropes, lactotropes, lactotrope and thyrotrope lineages thyrotropes cell proliferation/survival Oct-1 (Off-l, NF-A1, [M] ubiquitous potentially lethal b POU2F1) Xoct-1 Ix] SpOct [Sl oogenesis and early embryo antisense blocks protein accumulation in embryo Pdm-I (nubbin, dpou-19) [D] both: gap-like pattern in early Pdm-1 and Pdm-2--Cell fate Pdm-2 (miti-mere, dpou-28) [D] embryo; peripheral sensory organs; specification in NB4 neuroblast neuroectoderm, neuroblasts; lineage ectoderm; Pdm-1--proliferation in wing; Pdm-1 only--throughout wing functions in hinge region of wing primordium disc Oct-2 (Otf-2, NF-A2, [M] B cells; alternative splice forms in neonatal lethal; terminal POU2F2) nervous system differentiation of B cells is affected Skn-la/i (Oct-11, Epoc-1, [M] skin (keratinocytes) differentiation and wound healing c Otf-1 l, Pou2F3) Xnrl-16/21 [X] III Brn-1 (Otf-8, POU3F3) [MI all levels of CNS in embryo and not reported adult--more restricted in adult; intestine, kidney zp-12 lzl overlapping expression in embryonic not reported sp-23 {zfpoul) [ZI and adult nervous system; zpbrain 1,1 [Z] pronephric Wolffian duct Brn-2 (Otf-7, N-Oct-3, [M] all levels of CNS in embryo and postnatal lethal POU3F2) adult--more restricted expression in terminal differentiation and survival adult of supraoptic and paraventricular hypothalamic nuclei zp-47 [Z] all levels of CNS in embryo and adult not determined brain 1.2 [Z] all levels of CNS in embryo and adult not determined XLPOU 3 [Xl not described Brn-4 (RHS2, N-Oct-4, [M] all levels of CNS in embryo and not reported POU3F4, Oft-9) adult, pancrease, Rathke's pouch, whiskers, otic vesicle XLPOU 2 [M] Spemann's organizer, mesoderm in misexpression causes ectopic gastrula, neuroectoderm, neural expression of neural-specific plate, notochord, brain markers Tst-1/Oct-6/SCIP (Oft-6, [M] all levels of CNS, oligodendrocyte postnatal lethal; checkpoint control in POU3F1) precursors, Schwann cells, testes, peripheral myelination; terminal skin differentiation including migration zp50 d [Z] CNS: dynamic and complex expression during embryogenesis Cfla/drifter/ventral [D] Tracheal placodes; midline glia, wing embryonic: strong mutations are veinless disc, CNS (not neuroblasts), hindgut lethal; formation of tracheal tree, patterning of ventral ectoderm; migration but not survival of midline glia cells XLPOU Id Ix] 3.5-kb transcript---brain, eyes proliferation and differentiation of 2.5-kb transcript--skin wing CEH-6 [c] IV Unc-86 [c] nervous system lineage determination; terminal differentiation I-POU [D] nervous system Brn-3.0/Brn-3a (RDC- i, [M] CNS: midbrain, hindbrain, spinal cord neonatal lethal; swallowing defect; POU4F1) PNS: sensory ganglia uncoordinated; survival and terminal differentiation of sensory ganglia, compact formation of nucleus ambiguus red nucleus 1208 GENES& DEVELOPMENT Downloaded from genesdev.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press POU domain family values Table 1. (Continued) Class Facto# Expression Pattern Function Brn-3.1/Brn-3c (POU4F3) [M] CNS: restricted in midbrain, terminal differentiation of hair cells; hindbrain and spinal cord; PNS: null mice are deaf sensory ganglia brn-3.1 [Z] eye and brain Brn-3.2/Brn-3b (POU4F2) [M] CNS: midbrain, hindbrain, spinal cord terminal differentiation and survival PNS: sensory ganglia of retinal ganglion cells V Oct-3/4 (Oct-5, NF-A3, [M] maternal transcript in oocyte; not reported POU5F 1) totipotent and pluripotent cells during embryogenesis; restricts to primordial germ cells by E 11 in mouse Pou2 ~ [z] maternal transcript in oocyte; critical for early embryogenesis pluripotent cells in embryo; neural plate; rhombomeres 2 and 4 XLPOU-60 [X] maternal transcript in oocyte; dramatic decrease by early gastrulation (peak in oocyte and fertilized egg) XOct-25 [X] expressed from late oocyte through late gastrula/early neurula; expression peaks at early gastrula XLPOU-91 (oct91/oct92) expressed from midblastula through late neurula/early tailbud; peaks at gastrulation Sprm 1 [MI transiently in testes subtle effects on genetic fitness VI Brn-5 (Emb, Cns-1, mPOU, [M] CNS: broadly expressed not reported POU6F1) pouIcl [Z] Ubiquitous during embryogenesis; highest in CNS RPF-1 [Z] CNS: medial habenula, dorsal not reported thalamus, subset of retinal ganglion and amacrine cells Misc. CEH-18 [C] Gonadal sheath cells oocyte development, gonadal migration, epidermal differentiation in L 1 stage animals aSpecies of the factor is shown in square brackets at right of column. (C) C. elegans; (D) Drosophila; (M) mammalian; (S) sea urchin, (X) Xenopus; (Z) zebrafish. References for POU domain proteins not described in body of the text: Skn-la/i (Andersen et al.
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