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

作者：Kidder Benjamin L^*; Hu Gangqing; Cui Kairong; Zhao Keji^*

来源：Epigenetics and Chromatin, 2017, 10(1): 8.

DOI：10.1186/s13072-017-0115-7

• Embryonic stem cells
• SMYD5
• H4K20me3
• Repetitive DNA
• LTR
• LINE
• Pluripotent
• Epigenetics
• Chromatin
• Heterochromatin
• Genomics
• RNA-Seq
• ChIP-Seq
• Self-renewal
• Gene expression
• Embryoid body
• Differentiation
• Histone methyltransferase

Background: 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.
Results: 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 HP1a, 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.
Conclusions: Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin.

• 出版日期2017-2-23
• 单位NIH