Influence of Chromatin Structure on the Binding of Transcription Factors to DNA

Hager, Gordon L.; Archer, Trevor; Fragoso, Gilberto; Bresnick, Emery H.; Tsukagoshi, Y.; John, Sam; Smith, Catharine L.

doi:10.1101/sqb.1993.058.01.010

Cited by 49 publications

(31 citation statements)

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“…Recruitment of hSwi/ Snf activity by GR could also be detected by changes in restriction enzyme access [change in fractional cleavage, ⌬F(x)] in the B nucleosome region of MMTV. An increase in SacI access has been observed in vivo in the presence of dexamethasone (14,19,34) and in vitro with GR, extracts, and ATP (13). hSwi/Snf remodeling in the presence of ATP resulted in a slight increase in SacI access (Fig.…”

Section: Fig 2 Effect Of Atp On Binding Of Gr To Mmtv Chromatin (Amentioning

confidence: 99%

ATP-Dependent Mobilization of the Glucocorticoid Receptor during Chromatin Remodeling

Fletcher

Xiao

Mautino

et al. 2002

Molecular and Cellular Biology

123

101

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Chromatin remodeling by the glucocorticoid receptor (GR) is associated with activation of transcription at the mouse mammary tumor virus (MMTV) promoter. We reconstituted this nucleoprotein transition with chromatin assembled on MMTV DNA. The remodeling event was ATP dependent and required either a nuclear extract from HeLa cells or purified human Swi/Snf. Through the use of a direct interaction assay (magnetic bead pull-down), we demonstrated recruitment of human Swi/Snf to MMTV chromatin by GR. Unexpectedly, we found that GR is actively displaced from the chromatin template during the remodeling process. ATPdependent GR displacement was reversed by the addition of apyrase and was specific to chromatin templates. The disengagement reaction could also be induced with purified human Swi/Snf. Although GR apparently dissociated during chromatin remodeling by Swi/Snf, it participated in binding of the secondary transcription factor, nuclear factor 1. These results are paralleled by a recent discovery that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment in living cells. Both the in vitro and in vivo results are consistent with a dynamic model (hit and run) in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, facilitates transcription factor binding, and is simultaneously lost from the template.The regulation of transcription by nuclear receptors is intimately associated with reorganization of the chromatin structures of target promoters. Receptors interact, either directly or indirectly, with a variety of chromatin-remodeling factors and recruit these activities for chromatin modification in the vicinity of the hormone response elements (HREs). There are two general classes of chromatin-remodeling factors: those that covalently modify components of the nucleoprotein structure (including histone acetylases and deacetylases, methylases, and kinases) (31, 45) and a second group comprised of ATP-dependent nucleosome-remodeling proteins, collectively referred to as the Swi/Snf family of factors (22,23,35,36,51,54).The current paradigm suggests that the purpose of these chromatin-modifying activities is to reorganize the nucleoprotein structures of regulated genes to provide greater access for both site-specific promoter binding proteins and general (or basal) transcription factors, both of which are excluded from their binding sites in nonremodeled chromatin. The nuclear receptors appear to be members of a restricted group of activators (pioneer proteins) with the ability to bind chromatin and initiate the remodeling process (18,26,27,44,48,49).A parallel theme of this model is the concept of a stable initiation complex. Steroid receptors, such as the glucocorticoid (GR), progesterone (PR), and estrogen receptors, require ligand to bind DNA and are believed to assist in the formation of large, multifactor complexes that reside on the template in the continued presence of hormone (55). By using a receptor tagged with a green...

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Section: Fig 2 Effect Of Atp On Binding Of Gr To Mmtv Chromatin (Amentioning

confidence: 99%

ATP-Dependent Mobilization of the Glucocorticoid Receptor during Chromatin Remodeling

Fletcher

Xiao

Mautino

et al. 2002

Molecular and Cellular Biology

123

101

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“…Early studies developed important concepts regarding the impact of nucleosome positioning on protein-chromatin interactions (1), and more recently, ChIP technology (2) ushered in an explosive increase in information on the distribution of histone modifications and nucleosomes genome-wide (3). However, many questions remain unanswered regarding how higher-order chromatin structures are established and regulated.…”

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confidence: 99%

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

Kim

Bultman

Kiefer

et al. 2009

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

115

109

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The dynamic packaging of DNA into chromatin is a fundamental step in the control of diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote the formation of higher-order chromatin loops, the co-regulator machinery mediating loop assembly and disassembly is unknown. Using mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate that the Brg1 mutation abrogated a cell type-specific loop between the ␤-globin locus control region and the downstream ␤major promoter, despite trans-acting factor occupancy at both sites. By contrast, distinct loops were insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided additional evidence that BRG1 functions early in chromatin domain activation to mediate looping. Although the paradigm in which chromatin remodelers induce nucleosome structural transitions is well established, our results demonstrating an essential role of BRG1 in the genesis of specific chromatin loops expands the repertoire of their functions.chromatin ͉ erythroid ͉ GATA-1 ͉ globin ͉ transcription I ntegral to the developmental emergence of specialized cell types is the establishment of cell type-specific chromatin structures. Early studies developed important concepts regarding the impact of nucleosome positioning on protein-chromatin interactions (1), and more recently, ChIP technology (2) ushered in an explosive increase in information on the distribution of histone modifications and nucleosomes genome-wide (3). However, many questions remain unanswered regarding how higher-order chromatin structures are established and regulated.Nucleosomal filaments assemble into 30-nm fibers, which fold into higher-order loops (4). Chromosome conformation capture (3C) (5) studies have provided evidence for looping in response to trans-acting factor binding to chromatin (6-10). Key regulators of erythropoiesis-GATA-1 (11, 12), erythroid Krüppel-like factor (EKLF) (13), and the GATA-1-coregulator friend of GATA-1 (FOG-1) (14)-induce looping at the ␤-globin locus, in which the proximity of the locus control region (LCR) relative to a distant promoter increases (15, 16). The E-protein-interacting factor NL1/ Ldb1 also occupies the LCR and promotes looping (17). However, the role of chromatin modifying and remodeling co-regulators in looping is largely unexplored.Histone acetylation counteracts higher-order folding of chromatin templates in vitro (18), and broad acetylation characterizes active chromatin domains (19,20). Thus, it seems likely that histone acetylases and deacetylases are components of the looping machinery. As methylation of histone H3 at lysine 9 serves as a ligand that mediates heterochromatin protein 1 binding during heterochromatin assembly (21-23), the relevant methyltransferases might control looping. Although chromatin remodeling complexes, such as switch/sucrose nonfermentable (SWI/SNF), induce nucleosome structural transitions and a...

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“…The mouse mammary tumor virus (MMTV) promoter represents a well-studied mammalian system in which chromatin structure and transcriptional activity have been intimately linked (5,18). In the absence of glucocorticoid, the MMTV promoter is incorporated into six regularly positioned nucleosomes (33).…”

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confidence: 99%

Histone H1 Phosphorylation by Cdk2 Selectively Modulates Mouse Mammary Tumor Virus Transcription through Chromatin Remodeling

Bhattacharjee¹,

Banks

Trotter

et al. 2001

Molecular and Cellular Biology

102

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Transcriptional activation of the mouse mammary tumor virus (MMTV) promoter by ligand-bound glucocorticoid receptor (GR) is transient. Previously, we demonstrated that prolonged hormone exposure results in displacement of the transcription factor nuclear factor 1 (NF1) and the basal transcription complex from the promoter, the dephosphorylation of histone H1, and the establishment of a repressive chromatin structure. We have explored the mechanistic link between histone H1 dephosphorylation and silencing of the MMTV promoter by describing the putative kinase responsible for H1 phosphorylation. Both in vitro kinase assays and in vivo protein expression studies suggest that in hormone-treated cells the ability of cdk2 to phosphorylate histone H1 is decreased and the cdk2 inhibitory p21 protein level is increased. To address the role of cdk2 and histone H1 dephosphorylation in the silencing of the MMTV promoter, we used potent cdk2 inhibitors, Roscovitine and CVT-313, to generate an MMTV promoter which is associated predominantly with the dephosphorylated form of histone H1. Both Roscovitine and CVT-313 block phosphorylation of histone H1 and, under these conditions, the GR is unable to remodel chromatin, recruit transcription factors to the promoter, or stimulate MMTV mRNA accumulation. These results suggest a model where cdk2-directed histone H1 phosphorylation is a necessary condition to permit GR-mediated chromatin remodeling and activation of the MMTV promoter in vivo.DNA in eukaryotic nuclei is highly packaged into chromatin by two molecules each of the core histone proteins H2A, H2B, H3, and H4 and one molecule of linker histone H1 (44). In addition, to the intrinsic stearic considerations of wrapping DNA around the histone octamer, the posttranslation modification of the core histones have come under increased scrutiny (22,44). Numerous studies support a strong link between transcriptional regulation and the remodeling of chromatin structure through the acetylation of core histones H3 and H4 (20, 40, 46). The acetylation of core histones in vivo is presumed to play a role in increasing the accessibility of transcription factors to the promoters of target genes (23). More recently, the Mi-2 ATPase complex, which contains chromatin remodeling activity, has been linked to both DNA methylation and histone deacetylation (39, 47).The role of histone H1 in the regulation of transcription is less clear, but there is evidence that histone H1 interacts differentially with transcriptionally active and inactive regions of chromatin (29). Indeed, studies in Xenopus and Tetrahymena thermophila have ruled out an exclusive role for histone H1 phosphorylation in chromatin condensation (31,36). However, other studies in mammals and T. thermophila have found a correlation between transcriptional activation and decreased amounts of histone H1 (9,12,14). Thus, it is plausible, given the role of histone H1 in the packaging of the nucleosome, that posttranslational modifications of this protein may also be involved in transcript...

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Influence of Chromatin Structure on the Binding of Transcription Factors to DNA

Cited by 49 publications

References 0 publications

ATP-Dependent Mobilization of the Glucocorticoid Receptor during Chromatin Remodeling

ATP-Dependent Mobilization of the Glucocorticoid Receptor during Chromatin Remodeling

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

Histone H1 Phosphorylation by Cdk2 Selectively Modulates Mouse Mammary Tumor Virus Transcription through Chromatin Remodeling

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