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SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE94086 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA368813

REPOSITORIES: GEO

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SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation [RNA-Seq]

Project description:Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone lysine 20 (H4K20me3) in pluripotency and development are largely unknown. Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation. SMYD5 bound regions are enriched with repetitive DNA elements. Knockdown of SMYD5 results in a global decrease of H4K20me3 levels, a redistribution of heterochromatin constituents including H3K9me3/2, G9a, and HP1α, and de-repression of endogenous retroelements. A loss of SMYD5-dependent silencing of heterochromatin nearby genic regions leads to upregulated expression of lineage-specific genes, thus contributing to the decreased self-renewal and accelerated differentiation of SMYD5-depeleted ES cells. Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin.

2017-06-12 | GSE94085 | GEO

SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation [ChIP-Seq]

2017-06-12 | GSE94033 | GEO

SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation

Project description:SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation

| PRJNA368813 | ENA

H4K20me3 methyltransferase SMYD5 controls heterochromatin and chromosome integrity during embryonic stem cell differentiation

Project description:Epigenetic regulation of chromatin states is thought to control gene expression programs during lineage specification. However, the roles of repressive histone modifications such as trimethylated histone lysine 20 (H4K20me3) in development and genome stability are largely unknown. Here, we show that depletion of SMYD5, a H4K20me3 methyltransferase, leads to decreased H4K20me3 and H3K9me3 ChIP-Seq levels, and de-repression of endogenous LTR/LINE elements during differentiation. SMYD5 depletion results in chromosomal aberrations and the formation of transformed cells that exhibit decreased H4K20me3 and H3K9me3 levels and an expression signature consistent with multiple human cancers. Moreover, dysregulated gene expression in SMYD5 cancer cells is associated with LTR/ERV elements and decreased H4K20me3. These findings implicate an important role for SMYD5 in maintaining chromosome integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during differentiation.

2018-02-13 | GSE94955 | GEO