HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells

Deng, Tao; Zhu, Zhengwei; Zhang, Shaofei; Leng, Fenfei; Cherukuri, Srujana; Hansen, Larry G.; Mariño-Ramírez, Leonardo; Meshorer, Eran; Landsman, David; Bustin, Michael

doi:10.1128/mcb.00435-13

Cited by 39 publications

(69 citation statements)

References 55 publications

(79 reference statements)

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“…However, in our study, we found a nucleosome located at nucleosome-free regions. These nucleosomes were also found in other limited digestion studies (27)(28)(29). The observation of these nucleosomes indicates that these nucleosomes are most accessible and can be further digested with higher MNase concentrations.…”

Section: Acute Deletion Of Baf250a Disrupted the Differentiationsupporting

confidence: 50%

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: 50%

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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“…For each genotype, two independent MEF clones (biological replicates) were used in every experiment, including DNase-seq and MNase-seq. Neuroprogenitors were prepared from embryonic stem cells differentiated along the neural lineage using a mouse dopaminergic neuron differentiation kit (R&D Systems) as described (Deng et al 2013).…”

Section: Preparation Of Primary Mouse Embryonic Fibroblasts (Mefs) Anmentioning

confidence: 99%

“…HMGNs have been shown to bind to chromatin with a short residence time, efficiently counteract the chromatin condensing activity of histone H1, and induce changes in chromatin structure (Bustin 2001;Rochman et al 2009). Chromatin immunoprecipitation studies revealed that HMGN1, one of the two major HMGN variants, colocalizes genome-wide with DHSs (Cuddapah et al 2011;Deng et al 2013); however, it is not clear whether HMGNs affect the organization of DHSs in chromatin.…”

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confidence: 99%

Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers

et al. 2015

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DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHS landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome-wide mapping of the DHSs in Hmgn1 −/− , Hmgn2 −/− , and Hmgn1 −/− n2 −/− MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHS landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress-responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHS landscape, and the transcription fidelity and is necessary to retain wildtype phenotypes. Our study provides insight into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins. [Supplemental material is available for this article.]Tissue-and developmental-specific gene expression is facilitated by the binding of transcription factors to unique DNA sequences at regulatory sites in chromatin, such as enhancers and promoters. At these sites, the organization of the nucleosomes is altered, rendering the DNA more accessible to regulatory factors and hypersensitive to digestion by various nucleases including DNase I. DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA and are used to identify regulatory sites in chromatin. The DHSs chromatin landscape is cell-type specific and dynamic, reflecting changes in the cellular transcription profile occurring during development, or as a consequence of genomic changes leading to altered cellular phenotypes (Gross and Garrard 1988;Boyle et al. 2008;Thurman et al. 2012;Calo and Wysocka 2013;Stergachis et al. 2013).The molecular mechanisms that establish and maintain DHSs and their role in gene expression are key questions in chromatin biology. DHSs are established by the combined action of transcription factors that bind dynamically to specific DNA sequences and 12 These authors contributed equally to this work.

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“…6,7 It can affect the expression of numerous genes and regulate cellular differentiation. 6,[8][9][10] Analysis of Hmgn1-deficient cells indicated that loss of Hmgn1 led to both upregulation and downregulation of gene expression. 9,11,12 During brain development, Hmgn1 could promote astrocyte differentiation of neural precursor cells through modulating of the responsiveness to ciliary neurotrophic factor.…”

Section: Introductionmentioning

confidence: 99%

“…6,[8][9][10] Analysis of Hmgn1-deficient cells indicated that loss of Hmgn1 led to both upregulation and downregulation of gene expression. 9,11,12 During brain development, Hmgn1 could promote astrocyte differentiation of neural precursor cells through modulating of the responsiveness to ciliary neurotrophic factor. 10 Simultaneously, Hmgn1 might also direct chondrocyte differentiation by influencing the expression of Sox9 gene.…”

Section: Introductionmentioning

confidence: 99%

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

Yang

Guo

et al. 2015

Cell Cycle

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HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells

Cited by 39 publications

References 55 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

Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

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