POU-domain proteins: structure and function of developmental regulators

Wegner, Michael; Drolet, Daniel; Rosenfeld, Michael G.

doi:10.1016/0955-0674(93)90015-i

Cited by 237 publications

(168 citation statements)

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“…To investigate whether this element controls the induction of TN promoter activity by POU-HD proteins, we tested the activity of two promoter constructs that either contain or lack the octamer motif (TN11 and TN12, respectively) in cotransfection experiments with expression constructs for three class III POU-HD proteins, Brn2, Brn4, and SCIP. These proteins are all expressed during early neural development (26). Only Brn2 activated the TN promoter in an octamer-dependent manner, and this induction occurred only in N2A cells, not in C6 or NIH 3T3 cells (Table 2 and data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…In our cotransfection experiments that examined the regulation of the TN promoter by Brn2, Brn4, and SCIP, only Brn2 activated the TN promoter in an octamer-dependent manner. Although uncovering this activity in cellular transfection experiments is not sufficient to establish that this POU-HD protein is a natural regulator of TN gene expression, many POU-HD proteins are expressed in the developing nervous system in patterns that correlate with the spatiotemporal expression of TN in neuroepithelial precursors and glial cell lineages (26). Moreover, in the adult, POU-HD proteins are expressed in neuroblastomas and glioblastomas, in which TN expression is prominent.…”

Section: Discussionmentioning

confidence: 99%

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Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Copertino

Edelman

Jones

1997

Proc. Natl. Acad. Sci. U.S.A.

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Tenascin (TN) is an extracellular matrix glycoprotein that is expressed in a characteristic spatiotemporal pattern during development and is up-regulated in the adult during tumorigenesis, wound healing, and nerve regeneration. In previous studies, we identified a promoter within the proximal 250 bp upstream of the mouse TN gene that contains several putative regulatory elements that are conserved among vertebrate TN genes. We have identified four different DNA elements within this promoter and show that they contribute in different ways to TN gene expression in NIH 3T3 fibroblasts, C6 glioma cells, and N2A neuroblastoma cells. These elements comprise a binding site for Krox proteins, one for nuclear factor 1, an octamer motif that binds POU-homeodomain proteins, and a novel TN control element. The nuclear factor 1 and TN control element had positive effects on TN promoter activity and formed similar DNAprotein complexes with nuclear extracts from all three cell lines. The Krox element had a negative effect on TN promoter activity in N2A cells, a positive effect in C6 cells, and no effect in NIH 3T3 cells. Two DNA binding complexes, one correlated with the negative and the other with the positive activities of the Krox element, were found to contain the protein Krox24. In cotransfection experiments, the octamer motif was required for induction of TN promoter activity by the POUhomeodomain protein Brn2 in N2A cells but was inactive in C6 cells. Consistent with these findings, N2A cells transfected with Brn2 formed octamer-binding complexes containing N-Oct3, the transcriptionally active form of Brn2, whereas complexes formed in C6 cells contained only N-Oct5A and N-Oct5B. Our results provide a striking example of the diversity of regulatory mechanisms that can be called forth by combining different promoter motifs with transcriptional activators or repressors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Copertino

Edelman

Jones

1997

Proc. Natl. Acad. Sci. U.S.A.

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“…POU domain proteins constitute a growing family of transcription factors that regulate the expression of developmental and tissue-specific genes in a wide range of eukaryotic organisms (Wegner et al 1993;Herr and Cleary 1995). A characteristic of POU domain proteins is their extraordinary versatility in recognizing diverse DNA elements.…”

Section: Discussionmentioning

confidence: 99%

“…This differential binding can lead to alternative uses of the synergistic activation domains (Holloway et al 1995). Oct-1 was identified originally by its recognition of the conserved octamer motif TAAAG-CAT found in the promoters of a number of tissue-specific and ubiquitously expressed genes (Wegner et al 1993;Herr and Cleary 1995). Oct-1 can also bind to the distinct TAATGAi^AT (i^=purine) motif in regulating the expression of the immediate-early genes of herpes simplex virus (Baumruker et al 1988;apRhys et al 1989).…”

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confidence: 99%

“…The nuclear receptors go a step further and recognize DNA elements with different spacings and polarities between the half-sites (Naar et al 1991;Umesono et al 1991;Kurokawa et al 1993). The POU domain family of transcription factors are perhaps the most remarkable in their ability to bind DNA as both monomers and dimers and in their ability to adopt diverse configurations (Wegner et al 1993;Herr and Cleary 1995). Part of this versatility derives from their unusual bipartite structure, consisting of a highly conserved -75 amino acid POUspecific domain (POUg), tethered by a linker of variable length and composition, to a 60-amino-acid homeodomain (POUH).…”

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confidence: 99%

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Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

Jacobson¹,

Leon-Del-Rio²,

Rosenfeld³

et al. 1997

Genes Dev.

195

145

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Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix al and in the loop between helices a3 and a4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.[Key Words: Crystal structure; Pit-1; POU-domain factors; dimerization; spacing; orientation] Received October 25, 1996; revised version accepted December 3, 1996.The expression of specific genes in cells is often governed by families of transcription factors harboring DNA-binding motifs. In eukaryotes, these factors often exhibit extraordinary versatility. For instance, the bZip and helix-loop-helix families of transcription factors bind to DNA as both homo-and heterodimers (Bexevanis and Vinson 1993;Glover and Harrison 1995). The nuclear receptors go a step further and recognize DNA elements with different spacings and polarities between the half-sites (Naar et al. 1991;Umesono et al. 1991;Kurokawa et al. 1993). The POU domain family of transcription factors are perhaps the most remarkable in their ability to bind DNA as both monomers and dimers and in their ability to adopt diverse configurations (Wegner et al. 1993;Herr and Cleary 1995). Part of this versatility derives from their unusual bipartite structure, consisting of a highly conserved -75 amino acid POUspecific domain (POUg), tethered by a linker of variable length and composition, to a 60-amino-acid homeodomain (POUH). The flexibility of the linker, in particular, allows the possibility of different relative spacings and orientations between the subdomains. This helps to exThese authors contributed equally to this work. "Corresponding author. Present address:

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Role of Oct-6 in Schwann cell differentiation

Meijer¹,

Jaegle²

1998

Microsc. Res. Tech.

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Research into the POU transcription factor Oct‐6 has been the focus of much current attention, in particular its role in Schwann cell development and differentiation. Based on published data and data presented here, we propose a model for Oct‐6 function at two distinct stages of Schwann cell maturation. First, Oct‐6 function is required in promyelin cells for their timely differentiation into myelinating cells. Second, Oct‐6 functions during myelination and is required for the proper downregulation of its own gene. While the first function of Oct‐6 is firmly established, the second function is still highly hypothetical. Experiments to establish a distinct role for Oct‐6 in late Schwann cell differentiation are discussed. Microsc. Res. Tech. 41:372–378, 1998. © 1998 Wiley‐Liss, Inc.

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POU-domain proteins: structure and function of developmental regulators

Cited by 237 publications

References 91 publications

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

Role of Oct-6 in Schwann cell differentiation

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