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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.

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81969 | GEO | 2016/05/27

SECONDARY ACCESSION(S): PRJNA323528

REPOSITORIES: GEO

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Genome-wide mapping of H4K20me3 in proliferating and senescent IMR90 cells.

Project description:Cellular senescence is a stable proliferation arrest and tumor suppressor mechanism. Abundance of histone modification, H4K20me3, has been reported to increase in senescent cells. Generally, H4K20me3 promotes formation of compacted transcriptionally silent constitutive heterochromatin, but its specific role in senescence is unknown. Here, we show that in senescent cells H4K20me3 is enriched at specific families of gene repeats (ZNFs, Olfactory Receptors, Protocadherins), and DNA sequences contained within senescence-associated heterochromatin (senescence-associated heterochromatin (SAHF)). Furthermore, in senescent cells, but not proliferating cells, H4K20me3 is also markedly enriched at bodies of repressed genes, including proliferation-promoting genes. Ectopic expression of SUV420H2, responsible for deposition of H4K20me3, reinforces senescence-associated proliferation arrest, and slows proliferation of transformed cells and tumorigenesis in vivo. These results indicate a dedicated role for H4K20me3 in control of nuclear organization and gene expression in senescent cells and stable senescence-associated proliferation arrest and tumor suppression.

2016-05-27 | GSE59316 | GEO

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

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

2020-11-13 | GSE130721 | GEO

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: Not available

| S-EPMC4960804 | biostudies-literature

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 regulates pluripotent embryonic stem cells [ChIP-seq]

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

| PRJNA541174 | ENA

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

ChIP-SEQ of H4K20me3 in BCSCsSETD4 and BCSCsGFP

Project description:We report the ChIP-SEQ results of H4K20me3 in BCSCsSETD4 and BCSCsGFP. To explore epigenetic regulation by H4K20me3 in BCSC quiescence, we performed chromatin immunoprecipitation sequencing (ChIP-seq) using BCSCsSETD4 and BCSCsGFP. Quiescent BCSCsSETD4 showed marked enrichment of H4K20me3 modifications relative to BCSCsGFP.

2019-10-25 | GSE123841 | GEO

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