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

Overview of attention for article published in Epigenetics & Chromatin, February 2017
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Title
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation
Published in
Epigenetics & Chromatin, February 2017
DOI 10.1186/s13072-017-0115-7
Pubmed ID
Authors

Benjamin L. Kidder, Gangqing Hu, Kairong Cui, Keji Zhao

Abstract

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 4 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 perturbed differentiation of SMYD5-depleted ES cells. Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin.

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Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 51 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 22%
Researcher 9 18%
Student > Master 6 12%
Student > Doctoral Student 5 10%
Professor 3 6%
Other 5 10%
Unknown 12 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 39%
Agricultural and Biological Sciences 9 18%
Medicine and Dentistry 5 10%
Immunology and Microbiology 3 6%
Unspecified 1 2%
Other 0 0%
Unknown 13 25%