Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
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DOI：
10.1093/dnares/dsv013
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Ko MS
中科院分区：
文献类型：
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作者：
Akiyama T;Xin L;Oda M;Sharov AA;Amano M;Piao Y;Cadet JS;Dudekula DB;Qian Y;Wang W;Ko SB;Ko MS
小鼠胚胎干细胞（mESC）具有在培养中维持正常基因组稳定性和核型的显著能力。我们先前表明，不频繁的Zscan4表达爆发（Z4事件）对于维持mESC中的端粒长度和基因组稳定性是重要的。然而，Z4事件的分子细节仍不清楚。在这里，我们表明，Z4事件涉及意想不到的转录去抑制在异染色质区域，通常保持沉默。在Z4事件期间，我们看到异染色质的快速去阻遏和再阻遏导致转录的爆发，这与瞬时组蛋白高乙酰化和DNA去甲基化、围绕核仁的着丝粒周围异染色质的聚集以及激活和阻遏的染色质重塑复合物的积累相一致。这种基于异染色质的转录活性表明，mESC可能至少部分地通过瞬时重置其异染色质来维持其非凡的基因组稳定性。
Mouse embryonic stem cells (mESCs) have a remarkable capacity to maintain normal genome stability and karyotype in culture. We previously showed that infrequent bursts of Zscan4 expression (Z4 events) are important for the maintenance of telomere length and genome stability in mESCs. However, the molecular details of Z4 events remain unclear. Here we show that Z4 events involve unexpected transcriptional derepression in heterochromatin regions that usually remain silent. During a Z4 event, we see rapid derepression and rerepression of heterochromatin leading to a burst of transcription that coincides with transient histone hyperacetylation and DNA demethylation, clustering of pericentromeric heterochromatin around the nucleolus, and accumulation of activating and repressive chromatin remodelling complexes. This heterochromatin-based transcriptional activity suggests that mESCs may maintain their extraordinary genome stability at least in part by transiently resetting their heterochromatin.