Nuclear Factor 1 Is Required for Both Hormone-Dependent Chromatin Remodeling and Transcriptional Activation of the Mouse Mammary Tumor Virus Promoter

Hebbar, Pratibha B.; Archer, Trevor

doi:10.1128/mcb.23.3.887-898.2003

Cited by 53 publications

(50 citation statements)

References 60 publications

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“…Once recruited, this complex allows the initiation of the chromatin remodeling process, which may in turn stabilize the DNA binding of GR and NЈNRSF and promote the activation of gene transcription. This mode of cooperative function is consistent with recent studies demonstrating that in the glucocorticoid inducible MMTV promoter, recruitment of the BRG1 remodeling complex requires the simultaneous participation of GR and the transcription factor NF1 (52).…”

Section: Discussionsupporting

confidence: 77%

Dual Role of NRSF/REST in Activation and Repression of the Glucocorticoid Response

Abramovitz

Shapira

Ben-Dror

et al. 2008

Journal of Biological Chemistry

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Restriction of glutamine synthetase to the nervous system is mainly achieved through the mutual function of the glucocorticoid receptor and the neural restrictive silencing factor, NRSF/ REST. Glucocorticoids induce glutamine synthetase expression in neural tissues while NRSF/REST represses the hormonal response in non-neural cells. NRSF/REST is a modular protein that contains two independent repression domains, at the N and C termini of the molecule, and is dominantly expressed in nonneural cells. Neural tissues express however splice variants, REST4/5, which contain the repression domain at the N, but not at the C terminus of the molecule. Here we show that full-length NRSF/REST or its C-terminal domain can inhibit almost completely the induction of gene transcription by glucocorticoids. By contrast, the N-terminal domain not only fails to repress the hormonal response but rather stimulates it markedly. The inductive activity of the N-terminal domain is mediated by hBrm, which is recruited to the promoter only in the concomitant presence of GR. Importantly, a similar inductive activity is also exerted by the splice variant REST4. These findings raise the possibility that NRSF/REST exhibits a dual role in regulation of glutamine synthetase. It represses gene induction in nonneural cells and enhances the hormonal response, via its splice variant, in the nervous system.

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Section: Discussionsupporting

confidence: 77%

Dual Role of NRSF/REST in Activation and Repression of the Glucocorticoid Response

Abramovitz

Shapira

Ben-Dror

et al. 2008

Journal of Biological Chemistry

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“…A likely explanation is that these TFs act in different cellular contexts or have roles in vivo at these enhancers, such as remodeling chromatin, that are not required for activating transcription in our plasmid-based assay. Consistent with the latter notion, the list includes three Fox family TFs (Foxo4, Foxp3, and Foxd1), which act as pioneer factors that open chromatin during genomic enhancer activation (72)(73)(74), and two NFI TFs (NFIX and NFIC) that interact with histones (75,76) and contribute to remodeling of nucleosome architecture (77,78). The remaining two TFs (Myb and AP-2) have plausible roles in early adipocyte differentiation, regulating the final cell division (79,80) and repressing an alternate cell fate (81), respectively.…”

Section: Elements In the Sequence Flanking Pparγ Motifs Strongly Affectmentioning

confidence: 92%

Systematic dissection of genomic features determining transcription factor binding and enhancer function

Grossman

Zhang

Wang

et al. 2017

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

164

142

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Enhancers regulate gene expression through the binding of sequence-specific transcription factors (TFs) to cognate motifs. Various features influence TF binding and enhancer function-including the chromatin state of the genomic locus, the affinities of the binding site, the activity of the bound TFs, and interactions among TFs. However, the precise nature and relative contributions of these features remain unclear. Here, we used massively parallel reporter assays (MPRAs) involving 32,115 natural and synthetic enhancers, together with high-throughput in vivo binding assays, to systematically dissect the contribution of each of these features to the binding and activity of genomic regulatory elements that contain motifs for PPARγ, a TF that serves as a key regulator of adipogenesis. We show that distinct sets of features govern PPARγ binding vs. enhancer activity. PPARγ binding is largely governed by the affinity of the specific motif site and higher-order features of the larger genomic locus, such as chromatin accessibility. In contrast, the enhancer activity of PPARγ binding sites depends on varying contributions from dozens of TFs in the immediate vicinity, including interactions between combinations of these TFs. Different pairs of motifs follow different interaction rules, including subadditive, additive, and superadditive interactions among specific classes of TFs, with both spatially constrained and flexible grammars. Our results provide a paradigm for the systematic characterization of the genomic features underlying regulatory elements, applicable to the design of synthetic regulatory elements or the interpretation of human genetic variation.gene regulation | transcription factor binding | systems biology

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“…Earlier studies demonstrated that MBD1 partners with the p150 subunit of chromatin assembly factor 1 to form a multiprotein complex that also contains HP1a, suggesting a role for MBD1 in methylation-mediated transcriptional repression and inheritance of epigenetically determined chromatin states (34). A role for NF1 in chromatin remodeling, in addition to its directly enhancing transcriptional effect, has been reported by Hebbar et al (35). NF1 interacts with a variety of coactivator or cosuppressor proteins in a cell-type-and/or promoter-specific manner (21).…”

Section: Figurementioning

confidence: 93%

Epigenetic regulation of 11β-hydroxysteroid dehydrogenase type 2 expression

Alikhani-Koopaei¹,

Fouladkou²,

Frey³

et al. 2004

J. Clin. Invest.

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The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11β-hydroxyglucocorticoids. Variable activity of 11βHSD2 is relevant for blood pressure control and hypertension. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for the rigorous control of expression of the gene encoding 11βHSD2, HSD11B2. CpG islands covering the promoter and exon 1 of HSD11B2 were found to be densely methylated in tissues and cell lines with low expression but not those with high expression of HSD11B2. Demethylation induced by 5-aza-2′-deoxycytidine and procainamide enhanced the transcription and activity of the 11βHSD2 enzyme in human cells in vitro and in rats in vivo. Methylation of HSD11B2 promoter-luciferase constructs decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including those for Sp1/Sp3, Arnt, and nuclear factor 1 (NF1) diminished their DNA-binding activity. Herein NF1 was identified as a strong HSD11B2 stimulatory factor. The effect of NF1 was dependent on the position of CpGs and the combination of CpGs methylated. A methylated-CpG-binding protein complex 1 transcriptional repression interacted directly with the methylated HSD11B2 promoter. These results indicate a role for DNA methylation in HSD11B2 gene repression and suggest an epigenetic mechanism affecting this gene causally linked with hypertension.

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Nuclear Factor 1 Is Required for Both Hormone-Dependent Chromatin Remodeling and Transcriptional Activation of the Mouse Mammary Tumor Virus Promoter

Cited by 53 publications

References 60 publications

Dual Role of NRSF/REST in Activation and Repression of the Glucocorticoid Response

Dual Role of NRSF/REST in Activation and Repression of the Glucocorticoid Response

Systematic dissection of genomic features determining transcription factor binding and enhancer function

Epigenetic regulation of 11β-hydroxysteroid dehydrogenase type 2 expression

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