Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1

Hu, Gangqing; Schones, Dustin E.; Cui, Kairong; Ybarra, River; Northrup, Daniel; Tang, Qingsong; Gattinoni, Luca; Restifo, Nicholas P.; Huang, Suming; Zhao, Keji

doi:10.1101/gr.121145.111

Cited by 166 publications

(185 citation statements)

References 54 publications

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“…We then analyzed the nucleosome profile at the binding sites of chromatin insulators such as CTCF and REST. Consistent with previous reports (25,26), nucleosomes were well positioned at the binding sites of CTCF and the REST repressor protein in both WT and BAF250a KO ES cells (Fig. 2, A and B), indicating successful mapping of nucleosomes.…”

Section: Acute Deletion Of Baf250a Disrupted the Differentiationsupporting

confidence: 78%

BAF250a Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation

Lei

West

Yan

et al. 2015

Journal of Biological Chemistry

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Background: How BAF250a regulates nucleosome configuration in ES cells is not clear. Results: BAF250a regulates nucleosome occupancy and H3K27me3 to control gene expression during ES cell differentiation. Conclusion: BAF250a plays a key role in poised chromatin regulation. Significance: Understanding the mechanisms of chromatin remodeling in poised chromatin regulation provides epigenetic insights into ES cell differentiation.

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Section: Acute Deletion Of Baf250a Disrupted the Differentiationsupporting

confidence: 78%

BAF250a Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation

Lei

West

Yan

et al. 2015

Journal of Biological Chemistry

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“…In agreement with our results, kinetic studies in which the INF-b enhancer was artificially relocalized at a distance from its target promoter found that looping between them was dependent on transcription factors and preceded recruitment of coactivators and Pol II (Nolis et al 2009). Moreover, it is known that GATA1 chromatin occupancy is not dependent on BRG1 on a genome-wide scale (Hu et al 2011). Nevertheless, our data seem to contrast with the finding of early recruitment of BRG1 to globin loci before maximal GATA1 occupancy and looping in G1E cells (Kim et al 2009).…”

Section: Ldb1 Is a Transcription Coactivatorcontrasting

confidence: 56%

Role of LDB1 in the transition from chromatin looping to transcription activation

2014

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Many questions remain about how close association of genes and distant enhancers occurs and how this is linked to transcription activation. In erythroid cells, lim domain binding 1 (LDB1) protein is recruited to the b-globin locus via LMO2 and is required for looping of the b-globin locus control region (LCR) to the active b-globin promoter. We show that the LDB1 dimerization domain (DD) is necessary and, when fused to LMO2, sufficient to completely restore LCR-promoter looping and transcription in LDB1-depleted cells. The looping function of the DD is unique and irreplaceable by heterologous DDs. Dissection of the DD revealed distinct functional properties of conserved subdomains. Notably, a conserved helical region (DD4/5) is dispensable for LDB1 dimerization and chromatin looping but essential for transcriptional activation. DD4/5 is required for the recruitment of the coregulators FOG1 and the nucleosome remodeling and deacetylating (NuRD) complex. Lack of DD4/5 alters histone acetylation and RNA polymerase II recruitment and results in failure of the locus to migrate to the nuclear interior, as normally occurs during erythroid maturation. These results uncouple enhancer-promoter looping from nuclear migration and transcription activation and reveal new roles for LDB1 in these processes.

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“…Recent genome-wide studies of nucleosome dynamics and occupancy in differentiating ES cells and in comparing ES cells, iPSCs, NPCs, MEFs, and other somatic cells revealed that differences in occupancy specific to cell type and developmental stage are readily seen locally over small regions of the genome (TSS, specific genes) (62)(63)(64)(65). However, large (megabase) domains of differential occupancy between cell types were not observed in mammalian cells although they were observed in yeast.…”

Section: Discussionmentioning

confidence: 99%

Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination

Pulivarthy

Lion

Kuzu

et al. 2016

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

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We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineagespecific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase. These changes result in establishment of a specific chromatin organization at the RSS that facilitates accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse embryonic fibroblasts the coding segment is depleted of nucleosomes, which instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also find large-scale variations of nucleosome density over hundreds of kilobases, delineating chromosomal domains within IgH, in a cell typedependent manner. These findings suggest that developmentally regulated changes in nucleosome location and occupancy, in addition to the known chromatin modifications, play a fundamental role in regulating V(D)J recombination. Nucleosome positioning-which has previously been observed to vary locally at individual enhancers and promoters-may be a more general mechanism by which cells can regulate the accessibility of the genome during development, at scales ranging from several hundred base pairs to many kilobases.T he diverse repertoire of antigen receptors in vertebrates is generated by an ordered series of somatic site-specific DNA rearrangement events, collectively termed V(D)J recombination. Antigen receptor genes are assembled from V, D, and J gene segments organized into seven different loci [T-cell receptor (TCR) α, β, γ, and δ, and Ig H, κ, and λ], each of which undergoes a series of recombination reactions to generate a functional TCR or B-cell receptor (BCR) (1, 2) Rearrangement is lineage-specific, such that BCR genes are fully rearranged only in B cells and TCR genes are assembled only in T cells. Rearrangement also occurs in a preferred temporal order. For example, at the human and murine IgH loci, joining of D to J segments precedes V to DJ joining, and IgH joining precedes joining at Igκ (or Igλ) (3). In addition, recombination at several loci shows "allelic exclusion": Functional VDJH or VJκ/Jλ joining occurs only on one allele (4).Recombination is initiated by the lymphocyte-specific recombination activating gene (RAG)1/RAG2 endonuclease. RAG1/2 cleaves at the recombination signal sequences (RSSs) flanking all antigen receptor gene segments. The consensus RSS consists of a heptamer sequence directly adjacent to the coding element and an A/T-rich nonamer separated from the heptamer by a spacer region of conserved length (12 or 23 bp) but relatively nonconserved sequence. The broken ends are then joined with the aid of DNA repair proteins,...

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Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1

Cited by 166 publications

References 54 publications

BAF250a Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation

BAF250a Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation

Role of LDB1 in the transition from chromatin looping to transcription activation

Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination

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