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首页> 外文期刊>Epigenetics & Chromatin >SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation
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SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation

机译：SMYD5调节H4K20me3标记的异染色质以保护ES细胞自我更新并防止假性分化

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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 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. Conclusions Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin.
机译：背景技术染色质状态的表观遗传调控被认为可以控制胚胎干（ES）细胞的自我更新和分化。但是，在多能性和发育中，诸如三甲基化组蛋白4赖氨酸20（H4K20me3）等抑制性组蛋白修饰的作用尚不清楚。结果在这里，我们显示了组蛋白赖氨酸甲基转移酶SMYD5在异染色质区域介导H4K20me3。 SMYD5的耗尽会导致自我更新受损，包括OCT4靶标的表达失调和分化受到干扰。 SMYD5绑定区域富含重复的DNA元素。击倒SMYD5会导致H4K20me3水平整体下降，异染色质成分（包括H3K9me3 / 2，G9a和HP1α）的重新分布以及内源性逆转录元素的抑制。 SMYD5依赖的异染色质附近的基因区域的沉默的丢失导致谱系特异性基因的表达上调，从而有助于减少SMYD5耗尽的ES细胞的自我更新和扰动分化。结论总而言之，这些发现暗示了SMYD5在调节ES细胞自我更新和H4K20me3标记的异染色质中的作用。

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