Setting the Boundaries of Chromatin Domains and Nuclear Organization

Labrador, Mariano; Corcés, Victor G.

doi:10.1016/s0092-8674(02)01004-8

Cited by 201 publications

(144 citation statements)

References 19 publications

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“…A structural model proposes that the properties of the insulators result from their relationship with the organization of higher-order chromatin structures (Labrador and Corces, 2002). Experiments performed on a Drosophila insulator identified in a retroelement called gypsy help to illustrate this model.…”

Section: Insulators and Higher-order Chromatin Structuresmentioning

confidence: 99%

Insulators are fundamental components of the eukaryotic genomes

Brasset

Vaury

2005

Heredity

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The properties of cis-regulatory elements able to influence gene transcription over large distances have led to the hypothesis that elements called insulators should exist to limit the action of enhancers and silencers. During the last decades, insulators have been identified in many eukaryotes from yeast to human. Insulators possess two main properties: (i) they can block enhancer-promoter communication ('enhancer blocker activity'), and (ii) they can prevent the spread of repressive chromatin ('barrier activity'). This review focuses on recent studies designed to elucidate the molecular mechanisms of the insulator function, and gives an overview of the critical role of insulators in nuclear organization and functional identity of chromatin. Heredity (2005) 94, 571-576.

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Section: Insulators and Higher-order Chromatin Structuresmentioning

confidence: 99%

Insulators are fundamental components of the eukaryotic genomes

Brasset

Vaury

2005

Heredity

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“…The regulation of eukaryotic gene expression in the context of chromatin is a complex event and is essential for numerous cellular processes (Lemon and Tjian, 2000;Orphanides and Reinberg, 2002;Labrador and Corces, 2002;Maniatis and Reed, 2002;Felsenfeld and Groudine, 2003;Roberts and Orkin, 2004). Maintenance, establishment, and modification of global chromatin organization and local chromatin structure are modulated by a large number of chromatin-binding proteins that generate transcriptionally permissive or repressed chromatin domains in response to environmental stimuli (Workman and Kingston, 1998;Peterson and Workman, 2000;Jones and Kadonaga, 2000;Wu and Grunstein, 2000;Wolffe and Hansen, 2001;Becker et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Chromatin Remodeling Complexes Interact Dynamically with a Glucocorticoid Receptor–regulated Promoter

Johnson

Elbi

Parekh

et al. 2008

MBoC

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Brahma (BRM) and Brahma-related gene 1 (BRG1) are the ATP-dependent catalytic subunits of the SWI/SNF family of chromatin-remodeling complexes. These complexes are involved in essential processes such as cell cycle, growth, differentiation, and cancer. Using imaging approaches in a cell line that harbors tandem repeats of stably integrated copies of the steroid responsive MMTV-LTR (mouse mammary tumor virus-long terminal repeat), we show that BRG1 and BRM are recruited to the MMTV promoter in a hormone-dependent manner. The recruitment of BRG1 and BRM resulted in chromatin remodeling and decondensation of the MMTV repeat as demonstrated by an increase in the restriction enzyme accessibility and in the size of DNA fluorescence in situ hybridization (FISH) signals. This chromatin remodeling event was concomitant with an increased occupancy of RNA polymerase II and transcriptional activation at the MMTV promoter. The expression of ATPase-deficient forms of BRG1 (BRG1-K-R) or BRM (BRM-K-R) inhibited the remodeling of local and higher order MMTV chromatin structure and resulted in the attenuation of transcription. In vivo photobleaching experiments provided direct evidence that BRG1, BRG1-K-R, and BRM chromatin-remodeling complexes have distinct kinetic properties on the MMTV array, and they dynamically associate with and dissociate from MMTV chromatin in a manner dependent on hormone and a functional ATPase domain. Our data provide a kinetic and mechanistic basis for the BRG1 and BRM chromatin-remodeling complexes in regulating gene expression at a steroid hormone inducible promoter. INTRODUCTIONThe eukaryotic genome is organized into higher order chromatin structures in the nucleus. The regulation of eukaryotic gene expression in the context of chromatin is a complex event and is essential for numerous cellular processes (Lemon and Tjian, 2000;Orphanides and Reinberg, 2002;Labrador and Corces, 2002;Maniatis and Reed, 2002;Felsenfeld and Groudine, 2003;Roberts and Orkin, 2004). Maintenance, establishment, and modification of global chromatin organization and local chromatin structure are modulated by a large number of chromatin-binding proteins that generate transcriptionally permissive or repressed chromatin domains in response to environmental stimuli (Workman and Kingston, 1998;Peterson and Workman, 2000;Jones and Kadonaga, 2000;Wu and Grunstein, 2000;Wolffe and Hansen, 2001;Becker et al., 2002). The association of linker histones and nonhistone and heterochromatin-specific proteins such as high mobility group proteins and HP1 play key roles in the generation of higher order chromatin structures (Arents et al., 1991; Luger et al., 1997;Bustin, 1999;Eissenberg and Elgin, 2000;Hill, 2001;Thomas and Travers, 2001;Woodcock and Dimitrov, 2001;Grewal and Elgin, 2002;Bianchi and Agresti, 2005;Bustin et al., 2005;Verschure et al., 2005). The stearically restricted environment presented by chromatin is in part overcome by multisubunit protein complexes that enzymatically regulate chromatin structure. These complexes can e...

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“…In several systems, boundary element (BE) sequences are employed to block heterochromatin spread (reviewed in Bell et al 2001;Labrador and Corces 2002). In S. cerevisiae, the right boundary element of HMRa has been characterized as a tRNA Thr gene (Donze and Kamakaka 2001).…”

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confidence: 99%

Histone H3 Lysine 36 Methylation Antagonizes Silencing in Saccharomyces cerevisiae Independently of the Rpd3S Histone Deacetylase Complex

Tompa

Madhani

2007

Genetics

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In yeast, methylation of histone H3 on lysine 36 (H3-K36) is catalyzed by the NSD1 leukemia oncoprotein homolog Set2. The histone deacetylase complex Rpd3S is recruited to chromatin via binding of the chromodomain protein Eaf3 to methylated H3-K36 to prevent erroneous transcription initiation. Here we identify a distinct function for H3-K36 methylation. We used random mutagenesis of histones H3 and H4 followed by a reporter-based screen to identify residues necessary to prevent the ectopic spread of silencing from the silent mating-type locus HMRa into flanking euchromatin. Mutations in H3-K36 or deletion of SET2 caused ectopic silencing of a heterochromatin-adjacent reporter. Transcriptional profiling revealed that telomere-proximal genes are enriched for those that display decreased expression in a set2D strain. Deletion of SIR4 rescued the expression defect of 26 of 37 telomere-proximal genes with reduced expression in set2D cells, implying that H3-K36 methylation prevents the spread of telomeric silencing. Indeed, Sir3 spreads from heterochromatin into neighboring euchromatin in set2D cells. Furthermore, genetic experiments demonstrated that cells lacking the Rpd3S-specific subunits Eaf3 or Rco1 did not display the anti-silencing phenotype of mutations in SET2 or H3-K36. Thus, antagonism of silencing is independent of the only known effector of this conserved histone modification.

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Setting the Boundaries of Chromatin Domains and Nuclear Organization

Cited by 201 publications

References 19 publications

Insulators are fundamental components of the eukaryotic genomes

Insulators are fundamental components of the eukaryotic genomes

Chromatin Remodeling Complexes Interact Dynamically with a Glucocorticoid Receptor–regulated Promoter

Histone H3 Lysine 36 Methylation Antagonizes Silencing in Saccharomyces cerevisiae Independently of the Rpd3S Histone Deacetylase Complex

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