Heterochromatin establishment during early mammalian development is regulated by pericentromeric RNA and characterized by non-repressive H3K9me3.

Heterochromatin establishment during early mammalian development is regulated by pericentromeric RNA and characterized by non-repressive H3K9me3.
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哺乳动物早期发育期间的异染色质建立受折内膜RNA的调节,并以非抑制性H3K9me3为特征。

DOI:
10.1038/s41556-020-0536-6
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发表时间:
2020-07
影响因子:
21.3
通讯作者:
Torres-Padilla ME
Torres-Padilla ME
中科院分区:
生物学1区
文献类型:
--
作者:
Burton A;Brochard V;Galan C;Ruiz-Morales ER;Rovira Q;Rodriguez-Terrones D;Kruse K;Le Gras S;Udayakumar VS;Chin HG;Eid A;Liu X;Wang C;Gao S;Pradhan S;Vaquerizas JM;Beaujean N;Jenuwein T;Torres-Padilla ME

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哺乳动物受精后,配子被重新编程以产生全能合子,这是一个涉及从头建立染色质结构域的过程。在着床前发育过程中发生的一个主要特征是组成性异染色质的急剧重塑,尽管其功能相关性尚不清楚。在这里,我们表明,异染色质的建立依赖于Suv39h酶的逐步表达和调节活性。强制过早获得组成型异染色质导致发育受损和表观遗传重编程,表明异染色质重塑对于受精时的自然重编程至关重要。我们发现,从头H3K9三甲基化受精后的父原核催化Suv39h2和pericentromeric RNA抑制Suv39h2的活性,减少H3K9me3。从头H3K9me3最初对基因表达是非抑制性的,但相反可以标记启动子以进行压缩。总的来说,我们揭示了组成型异染色质在重编程过程中的限制性传输的功能重要性和H3K9me3的非抑制作用。
Upon fertilization in mammals the gametes are reprogrammed to create a totipotent zygote, a process that involves de novo establishment of chromatin domains. A major feature occurring during preimplantation development is the dramatic remodeling of constitutive heterochromatin, although the functional relevance of this is unknown. Here we show that heterochromatin establishment relies on the stepwise expression and regulated activity of Suv39h enzymes. Enforcing precocious acquisition of constitutive heterochromatin results in compromised development and epigenetic reprogramming, demonstrating that heterochromatin remodeling is essential for natural reprogramming at fertilization. We find that de novo H3K9 trimethylation in the paternal pronucleus after fertilization is catalyzed by Suv39h2 and that pericentromeric RNAs inhibit Suv39h2 activity and reduce H3K9me3. De novo H3K9me3 is initially non-repressive for gene expression but instead can bookmark promoters for compaction. Overall, we uncover the functional importance for the restricted transmission of constitutive heterochromatin during reprogramming and a non-repressive role for H3K9me3.
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