Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules

Klemm, Juli D.; Rould, Mark A.; Aurora, Rajeev; Herr, Winship; Pabo, Carl O.

doi:10.1016/0092-8674(94)90231-3

Cited by 476 publications

(485 citation statements)

References 51 publications

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“…Both domains make specific contact with DNA through a helix-turnhelix structure and are connected by a variable linker of 15 to 56 amino-acids [15]. Regions outside the POU domain are not critical for DNA binding and exhibit little sequence conservation.…”

Section: Structure and Function Of Oct4mentioning

confidence: 99%

Stem cell pluripotency and transcription factor Oct4

et al. 2002

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Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of the 20th century. The dawn of the 21 st has brought forward great expectations in harnessing the power of totipotentcy in medicine. Through stem cell biology, it is possible to generate any parts of the human body by stem cell engineering. Considerable resources will be devoted to harness the untapped potentials of stem cells in the foreseeable future which may transform medicine as we know today. At the molecular level, totipotency has been linked to a singular transcription factor and its expression appears to define whether a cell should be totipotent. Named Oct4, it can activate or repress the expression of various genes. Curiously, very little is known about Oct4 beyond its ability to regulate gene expression. The mechanism by which Oct4 specifies totipotency remains entirely unresolved. In this review, we summarize the structure and function of Oct4 and address issues related to Oct4 function in maintaining totipotency or pluripotency of embryonic stem cells.

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Section: Structure and Function Of Oct4mentioning

confidence: 99%

Stem cell pluripotency and transcription factor Oct4

et al. 2002

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“…POU5F1 encodes a transcription factor which binds the octamer motif (ATGCAAAT) present in the promoter or enhancer regions of target genes [8,9]. Murine Pou5f1 is expressed in the embryonic stem cells (ESCs) and germ cells of the pregastrulation embryo to maintain an undifferentiated phenotype.…”

Section: Introductionmentioning

confidence: 99%

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

Möller

Stenman

Mandahl

et al. 2008

The Journal of Pathology

108

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The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino‐terminal domain and the POU5F1 carboxy‐terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild‐type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…The POU domain consists of two structurally independent subdomains: a 75-amino-acid aminoterminal region specific for this class of transcription factors (POU S ) and a 60-amino-acid carboxy-terminal homeodomain (POU H ). Both subdomains make specific contacts with DNA through a helix-turn-helix structure (17) and are connected by a variable linker that can vary from 15 to 56 amino acids (aa) in length.…”

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confidence: 99%

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Brehm

Ohbo

Schöler

1997

Molecular and Cellular Biology

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The POU transcription factor Oct-4 is expressed in totipotent and pluripotent cells of the early mouse embryo and the germ cell lineage. Transactivation capacities of regions flanking the DNA binding domain of Oct-4 were analyzed in undifferentiated and differentiated cell lines. The amino-and carboxy-terminal regions (N domain and C domain) fused to the Gal4 DNA binding domain both functioned as transactivation domains in all cell lines tested. However, the C domain failed to activate transcription in some cell lines in the context of the native protein. The underlying regulatory mechanism appears to involve the POU domain of Oct-4 and can discriminate between different POU domains, since constructs in which the C domain was instead fused to the POU domain of Pit-1 were again equally active in all cell lines. These results indicate that the C domain is subject to cell-type-specific regulation mediated by the Oct-4 POU domain. Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status. Since Oct-4 is expressed in a variety of distinct cell types during murine embryogenesis, these results suggest an additional regulatory mechanism for determining Oct-4 function in rapidly changing cell types during development.The octamer motif is a regulatory DNA element involved in both ubiquitous and cell-type-specific gene expression and is recognized by a family of eukaryotic transcription factors that share a homologous bipartite DNA binding domain, the POU domain (13,44,52,55). The POU domain consists of two structurally independent subdomains: a 75-amino-acid aminoterminal region specific for this class of transcription factors (POU S ) and a 60-amino-acid carboxy-terminal homeodomain (POU H ). Both subdomains make specific contacts with DNA through a helix-turn-helix structure (17) and are connected by a variable linker that can vary from 15 to 56 amino acids (aa) in length.Regions outside the POU domain are not critical for DNA binding and show little sequence conservation. In many cases,

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Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules

Cited by 476 publications

References 51 publications

Stem cell pluripotency and transcription factor Oct4

Stem cell pluripotency and transcription factor Oct4

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

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