Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement.

Peterson, Craig L.; Dingwall, Andrew K.; Scott, Matthew P.

doi:10.1073/pnas.91.8.2905

Cited by 382 publications

(261 citation statements)

References 20 publications

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“…As methylation of histone H3 at lysine 9 serves as a ligand that mediates heterochromatin protein 1 binding during heterochromatin assembly (21)(22)(23), the relevant methyltransferases might control looping. Although chromatin remodeling complexes, such as switch/sucrose nonfermentable (SWI/SNF), induce nucleosome structural transitions and alter nucleosome positioning (24,25), their role in looping is unknown.…”

mentioning

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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mentioning

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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“…For example, determination of the X-ray crystal structure of the histone octamer at high resolution has indicated that the C termini of histones are also flexible and may therefore be available for regulated interactions with DNA or other proteins (3, 4). Additionally, the more central regions of histones (especially those exposed to the surface) could easily be involved in interactions with DNA, histones, or other proteins in ways that affect transcription.Analysis of histone mutants has provided evidence that a complex of yeast proteins that includes SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3 may be required for transcriptional activators to overcome chromatin-mediated repression (11,30,55; see reference 77 for a review). The SNF/SWI complex is required for transcription of a large number of diversely regulated genes (see reference 77 for a review) and is also required for the function of several activators from S. cerevisiae and other organisms (40,56,84).…”

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confidence: 99%

“…Analysis of histone mutants has provided evidence that a complex of yeast proteins that includes SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3 may be required for transcriptional activators to overcome chromatin-mediated repression (11,30,55; see reference 77 for a review). The SNF/SWI complex is required for transcription of a large number of diversely regulated genes (see reference 77 for a review) and is also required for the function of several activators from S. cerevisiae and other organisms (40,56,84).…”

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A New Class of Histone H2A Mutations in Saccharomyces cerevisiae Causes Specific Transcriptional Defects In Vivo

Hirschhorn

Bortvin

Ricupero-Hovasse

et al. 1995

Molecular and Cellular Biology

106

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Nucleosomes have been shown to repress transcription both in vitro and in vivo. However, the mechanisms by which this repression is overcome are only beginning to be understood. Recent evidence suggests that in the yeast Saccharomyces cerevisiae, many transcriptional activators require the SNF/SWI complex to overcome chromatin-mediated repression. We have identified a new class of mutations in the histone H2A-encoding gene HTA1 that causes transcriptional defects at the SNF/SWI-dependent gene SUC2. Some of the mutations are semidominant, and most of the predicted amino acid changes are in or near the N-and C-terminal regions of histone H2A. A deletion that removes the N-terminal tail of histone H2A also caused a decrease in SUC2 transcription. Strains carrying these histone mutations also exhibited defects in activation by LexA-GAL4, a SNF/SWI-dependent activator. However, these H2A mutants are phenotypically distinct from snf/swi mutants. First, not all SNF/SWI-dependent genes showed transcriptional defects in these histone mutants. Second, a suppressor of snf/swi mutations, spt6, did not suppress these histone mutations. Finally, unlike in snf/swi mutants, chromatin structure at the SUC2 promoter in these H2A mutants was in an active conformation. Thus, these H2A mutations seem to interfere with a transcription activation function downstream or independent of the SNF/SWI activity. Therefore, they may identify an additional step that is required to overcome repression by chromatin.In eukaryotic cells, DNA is complexed with histones and other proteins into chromatin (see reference 75 for a review). The primary component of chromatin is the nucleosome, which consists of approximately 146 bp of DNA wrapped around an octamer of histones (two histone H2A-H2B dimers and one [H3-H4] 2 tetramer; see reference 75 for a review). A growing body of evidence from both in vivo and in vitro studies has shown that the structure of chromatin influences gene expression (see references 25 and 53 for reviews). Biochemical experiments have shown that histones can repress transcription in vitro (see reference 53 for a review) and that transcriptional activators can overcome this repression (21,41,45,79,81,82). In vivo experiments in Saccharomyces cerevisiae have shown that the loss of transcriptional activators or of activator binding sites can be suppressed by mutations in histone genes (27,30,37,57). These results suggest that one function of transcriptional activators in vivo is to antagonize chromatin-mediated repression.In vivo studies of histone mutants have also suggested that histones play a variety of roles in transcriptional regulation. Small deletions and point mutations that alter the flexible N-terminal tails of different yeast histones have been shown to cause specific changes in transcription (see reference 25 for a review). Analysis of deletions and single amino acid changes in the N-terminal region of histone H4 has demonstrated that certain changes in the H4 N terminus abolish repression of the yeast silent mating-...

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“…SWI (Switch) and SNF (Sucrose Non Fermenting) genes have been found to encode proteins that together assemble a large multisubunit complex required for the regulation of a specific group of inducible genes (Cairns et al 1994;Peterson et al 1994). A major clue to the molecular mechanisms by which the SWI/SNF activator complex functions came from a genetic screen for mutations of genes that would allow transcription from the HO gene in the absence of specific SWI genes .…”

Section: Activators and Repressors: Genetic Definition In S Cerevisiaementioning

confidence: 99%

Activators and repressors: making use of chromatin to regulate transcription

1997

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Metazoans and yeast use enzymes that modulate histone acetylation and nucleosomal integrity in order to regulate transcription. Repressor complexes deacetylate histones and stabilize nucleosomes. Activator complexes acetylate histones and disrupt nucleosomes. Variation in chromatin structure makes a major contribution to gene regulation. Here we discuss the enzymatic complexes and molecular machines that make use of chromatin to control transcription.

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Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement.

Cited by 382 publications

References 20 publications

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

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

A New Class of Histone H2A Mutations in Saccharomyces cerevisiae Causes Specific Transcriptional Defects In Vivo

Activators and repressors: making use of chromatin to regulate transcription

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