Mapping of the Transcriptional Repression Domain of the Lymphoid-specific Transcription Factor Oct-2A

Friedl, Erika M.; Matthias, Patrick

doi:10.1074/jbc.271.24.13927

Cited by 10 publications

(5 citation statements)

References 42 publications

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“…The removal of the inhibitory N-terminal region generates an Oct-2 mutant, which is both competent for Grg/TLE-mediated repression and has greatly elevated transcriptional activation properties, as previously demonstrated (15). This allowed us to determine whether repression could occur in the absence of OBF-1, on both the PORE-D and the OBF-1 excluding MORE motif.…”

Section: Resultssupporting

confidence: 66%

“…The ability to distinguish between different cis motifs suggested to us that the recruitment of Grg/TLE could occur through the POU domain. However, the N-terminal region of Oct has previously been shown as a repressor of a number of different promoters (15,16). To exclude the N-terminal repression region as being the Grg/TLE interacting domain, we assessed different deletion mutants of Oct-2.…”

Section: Resultsmentioning

confidence: 99%

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DNA-dependent conversion of Oct-1 and Oct-2 into transcriptional repressors by Groucho/TLE

Malin

Linderson

Almqvist

et al. 2005

Nucleic Acids Research

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POU domain proteins contain a bipartite DNA-binding element that can confer allosteric control of coactivator recruitment. Dimerization of Oct-1 and Oct-2 on palindromic response elements results in the conformational dependent inclusion or exclusion of the transcriptional coactivator OBF-1. In this paper, we demonstrate that Oct-1 and Oct-2 can function as transcriptional repressors by recruiting and physically interacting with members of the Grg/TLE family of corepressors. In accordance with a model of DNA induced cofactor assembly, and analogous to the recruitment of the OBF-1 coactivator, the different Grg/TLE members can discriminate between both Oct-1 and Oct-2, and the monomeric or dimeric nature of the POU/DNA complex.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

DNA-dependent conversion of Oct-1 and Oct-2 into transcriptional repressors by Groucho/TLE

Malin

Linderson

Almqvist

et al. 2005

Nucleic Acids Research

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“…The analysis of the activity of the deletion mutants of TTF-2 allowed us to map the repression domain in the region between amino acids 197 and 218 at the carboxyl terminus of the protein. As in the case of other transcriptional repressors (21)(22)(23), the repression domain of TTF-2 is rich in alanine and proline. At variance, however, of repressors such as Even-skipped and Kruppel that interact directly with TBP and the TFIIEb subunit, respectively (24,25), we exclude for TTF-2 a repression mechanism simply based on the interference with the basal transcription machinery, since we demonstrate that TTF-2 repression is promoter specific (this paper and (1)).…”

Section: Discussionmentioning

confidence: 87%

The Thyroid Transcription Factor 2 (TTF-2) Is a Promoter-Specific DNA-Binding Independent Transcriptional Repressor

Perrone

Magliano

Zannini³

et al. 2000

Biochemical and Biophysical Research Communications

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“…In addition to hPR, several other transcription factors have been shown to contain both activation and repression functions (2,3,8,15,17,21,34). Of particular relevance to our studies of hPRA, it has been shown in vitro that the ability of ROR␣ to repress transcription correlates with the ability of the inhibitory domain within ROR␣ to recruit the corepressors NCoR and SMRT (21).…”

Section: Discussionmentioning

confidence: 89%

The Opposing Transcriptional Activities of the Two Isoforms of the Human Progesterone Receptor Are Due to Differential Cofactor Binding

Giangrande

Kimbrel

Edwards

et al. 2000

Molecular and Cellular Biology

347

200

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The human progesterone receptor (PR) exists as two functionally distinct isoforms, hPRA and hPRB. hPRB functions as a transcriptional activator in most cell and promoter contexts, while hPRA is transcriptionally inactive and functions as a strong ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity. Although the precise mechanism of hPRA-mediated transrepression is not fully understood, an inhibitory domain (ID) within human PR, which is necessary for transrepression by hPRA, has been identified. Interestingly, although ID is present within both hPR isoforms, it is functionally active only in the context of hPRA, suggesting that the two receptors adopt distinct conformations within the cell which allow hPRA to interact with a set of cofactors that are different from those recognized by hPRB. In support of this hypothesis, we identified, using phage display technology, hPRA-selective peptides which differentially modulate hPRA and hPRB transcriptional activity. Furthermore, using a combination of in vitro and in vivo methodologies, we demonstrate that the two receptors exhibit different cofactor interactions. Specifically, it was determined that hPRA has a higher affinity for the corepressor SMRT than hPRB and that this interaction is facilitated by ID. Interestingly, inhibition of SMRT activity, by either a dominant negative mutant (C'SMRT) or histone deacetylase inhibitors, reverses hPRA-mediated transrepression but does not convert hPRA to a transcriptional activator. Together, these data indicate that the ability of hPRA to transrepress steroid hormone receptor transcriptional activity and its inability to activate progesterone-responsive promoters occur by distinct mechanisms. To this effect, we observed that hPRA, unlike hPRB, was unable to efficiently recruit the transcriptional coactivators GRIP1 and SRC-1 upon agonist binding. Thus, although both receptors contain sequences within their ligand-binding domains known to be required for coactivator binding, the ability of PR to interact with cofactors in a productive manner is regulated by sequences contained within the amino terminus of the receptors. We propose, therefore, that hPRA is transcriptionally inactive due to its inability to efficiently recruit coactivators. Furthermore, our experiments indicate that hPRA interacts efficiently with the corepressor SMRT and that this activity permits it to function as a transdominant repressor.

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Mapping of the Transcriptional Repression Domain of the Lymphoid-specific Transcription Factor Oct-2A

Cited by 10 publications

References 42 publications

DNA-dependent conversion of Oct-1 and Oct-2 into transcriptional repressors by Groucho/TLE

DNA-dependent conversion of Oct-1 and Oct-2 into transcriptional repressors by Groucho/TLE

The Thyroid Transcription Factor 2 (TTF-2) Is a Promoter-Specific DNA-Binding Independent Transcriptional Repressor

The Opposing Transcriptional Activities of the Two Isoforms of the Human Progesterone Receptor Are Due to Differential Cofactor Binding

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