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H4K20me3 methyltransferase SUV420H2 regulates pluripotent embryonic stem cells [ChIP-seq]

ABSTRACT: Heterochromatin, which is a densely packed chromatin state that is transcriptionally silent, is a critical regulator of gene expression. However, it is unclear how the repressive histone modification, H4K20me3, or the histone methyltransferase, SUV420H2, regulate embryonic stem (ES) cell fate by patterning the epigenetic landscape. Here, we observed a near complete genome-wide loss of H4K20me3 in SUV420H2 depleted ES cells, suggesting that SUV420H enzymes are paramount for establishing global H4K20me3 domains. We also found that SUV0420H2-bound regions are enriched with repetitive DNA elements. Together, these findings describe a novel role for SUV420H2 in regulating the chromatin landscape of ES cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE130721 | GEO | 2020/11/13

REPOSITORIES: GEO

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H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells

Project description:Heterochromatin, which is a densely packed chromatin state that is transcriptionally silent, is a critical regulator of gene expression. However, it is unclear how the repressive histone modification, H4K20me3, or the histone methyltransferase, SUV420H2, regulate embryonic stem (ES) cell fate by patterning the epigenetic landscape. Here, we report that depletion of SUV420H2 leads to a near complete loss of H4K20me3 genome-wide, dysregulated gene expression, and delayed ES cell differentiation. SUV420H2-bound regions are enriched with repetitive DNA elements, which are de-repressed in SUV420H2 knockout ES cells. Moreover, SUV420H2 regulation of H4K20me3-marked heterochromatin controls chromatin architecture, including fine-scale interactions between gene regulatory elements in pluripotent ES cells. SUV420H2 plays a critical role in stabilizing the three-dimensional (3D) chromatin landscape of ES cells, where loss of SUV420H2 results in A/B compartment switching, perturbed chromatin insulation, and altered chromatin interactions of pericentric heterochromatin, indicative of localized decondensation. In addition, depletion of SUV420H2 resulted in compromised interactions between H4K20me3 and gene regulatory regions. Together, these findings describe a novel role for SUV420H2 in regulating the chromatin landscape of ES cells.

2020-11-13 | GSE130723 | GEO

H4K20me3 methyltransferase SUV420H2 shapes the three-dimensional chromatin landscape of pluripotent embryonic stem cells [RNA-seq]

2020-11-13 | GSE130696 | GEO

SUV420H2 over-expression affects on gene expression in human breast cancer MDA-MB-231 cells

Project description:Analysis of breast cancer MDA-MB-231 cells stably over-expressing SUV420H2, a histone H4K20 methyltransferase. Several genes were significantly up- or down-regulated. Results provide insight into the molecular mechanism by which H4K20me3 contributes to gene expression. SUV420H2 stably over-expressing MDA-MB-231 cells were cloned. Then total RNA was extracted from the SUV420H2 over-expressing cells and the parental MDA-MB-231 cells.

2015-04-15 | E-GEOD-55947 | biostudies-arrayexpress

SUV420H2 over-expression affects on gene expression in human breast cancer MDA-MB-231 cells [MAA13355]

2015-04-15 | E-GEOD-56912 | biostudies-arrayexpress

H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells

Project description:H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells

| PRJNA541180 | ENA

SUV420H2 over-expression affects on gene expression in human breast cancer MDA-MB-231 cells

2015-04-15 | GSE55947 | GEO

SUV420H2 over-expression affects on gene expression in human breast cancer MDA-MB-231 cells [MAA13355]

2015-04-15 | GSE56912 | GEO

H4K20me3 co-localizes with activating histone modifications at transcriptionally dynamic regions in embryonic stem cells

Project description:Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. However, it is unknown whether another repressive histone modification, histone 4 lysine 20 trimethylation (H4K20me3), co-localizes with activating histone marks in ES cells. Here, we describe the previously uncharacterized coupling of the repressive H4K20me3 heterochromatin mark with the activating histone modifications H3K4me3 and histone 3 lysine 36 trimethylation (H3K36me3), and transcriptional machinery (RNA polymerase II; RNAPII), in ES cells. These newly described bivalent domains consisting of H3K4me3/H4K20me3 are predominantly located in intergenic regions and near transcriptional start sites of active genes, while H3K36me3/H4K20me3 are located in intergenic regions and within gene body regions of active genes. Global sequential ChIP, also termed reChIP-Seq, confirmed the simultaneous presence of H3K4me3 and H4K20me3 at the same genomic regions in ES cells. Genes containing H3K4me3/H4K20me3 exhibit decreased RNAPII pausing and are poised for deactivation of RNAPII binding during differentiation relative to H3K4me3 marked genes. An evaluation of transcription factor (TF) binding motif enrichment revealed that DNA sequence may play a role in shaping the landscape of these novel bivalent domains. Moreover, H3K4me3/H4K20me3 and H3K36me3/H4K20me3 bound regions are enriched with repetitive LINE and LTR elements.

2018-06-18 | GSE115907 | GEO

H4K20me3 methyltransferase SUV420H2 regulates pluripotent embryonic stem cells [ChIP-seq]

Project description:H4K20me3 methyltransferase SUV420H2 regulates pluripotent embryonic stem cells [ChIP-seq]

| PRJNA541174 | ENA

Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability.

Project description:Histone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although abundance of H4K20me3 increases during cellular senescence. Cellular senescence is a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we set out to better understand the function of H4K20me3 in senescence and tumor suppression.

2016-05-27 | GSE81969 | GEO

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