Appearance and heterochromatin localization of HP1α in early mouse embryos depends on cytoplasmic clock and H3S10 phosphorylation
Appearance and heterochromatin localization of HP1α in early mouse embryos depends on cytoplasmic clock and H3S10 phosphorylation
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DOI：
10.4161/cc.20705
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发表时间：
2012-06-01
期刊：
影响因子：
4.3
通讯作者：
Borsuk, Ewa
中科院分区：
文献类型：
--
作者：
Meglicki, Maciej;Teperek-Tkacz, Marta;Borsuk, Ewa
中心周组成型异染色质围绕着丝粒区域，对于着丝粒功能和染色单体凝聚力很重要。 HP1（异染色质蛋白 1）是酵母 Swi6 的同源物，已被证明对于正确的异染色质结构和功能是不可或缺的。在哺乳动物体细胞中，两种 HP1 亚型 HP1 α 和 HP1 β 持续存在于中心周异染色质中，直至 G 2 晚期，此时它们与异染色质解离。随后，它们在后期与异染色质重新结合。在单细胞小鼠胚胎中，中心周异染色质具有独特的结构和特征。它不会形成在体细胞中观察到的异染色质簇（称为染色中心）。相反，在两个原核中，它都围绕核仁前体（NBP），形成环状结构。这些区域在两个原核中均含有 HP1 β，但缺乏 HP1 α。在随后的间期中，HP1β 持续存在于异染色质中，直至囊胚阶段。目前尚不清楚 HP1 α 何时出现及其在早期小鼠胚胎中的功能。在这里，我们发现 HP1 α 首次出现在双细胞阶段的 S 期晚期，即中心周异染色质复制时。它的出现是在翻译层面上规定的。在双细胞胚胎中，可与这些区域结合的 HP1 α 的量受组蛋白 H3 (H3S10Ph) 丝氨酸 10 磷酸化的调节。 siRNA 消除 HP1 α 会干扰两细胞阶段着丝粒从 NPB 周围的异染色质到原染色中心的重新定位，但不影响着床前发育至囊胚阶段。
Pericentric constitutive heterochromatin surrounds centromeric regions and is important for centromere function and chromatid cohesion. HP1 (heterochromatin protein 1), a homolog of yeast Swi6, has been shown to be indispensible for proper heterochromatin structure and function. In mammalian somatic cells, two HP1 isoforms, HP1 alpha and HP1 beta, are constitutively present in pericentric heterochromatin until late G 2, when they dissociate from heterochromatin. Subsequently, they re-associate with heterochromatin at late anaphase. In one-cell mouse embryos, pericentric heterochromatin has a unique configuration and features. It does not form heterochromatin clusters observed in somatic cells and known as chromocenters. Instead, in both pronuclei, it surrounds nucleolar precursor bodies (NBPs), forming ring-like structures. These regions contain HP1 beta but lack HP1 alpha in both pronuclei. In subsequent interphases, HP1 beta is constitutively found in heterochromatin until the blastocyst stage. It is not known when HP1 alpha appears and what its function is in early mouse embryos. Here, we show that HP1 alpha appears for the first time at late S phase of two-cell stage, at the time when pericentric heterochromatin is replicated. Its appearance is regulated at the level of translation. In two-cell embryos, the amount of HP1 alpha that can bind to these regions is regulated by phosphorylation of serine 10 of histone H3 (H3S10Ph). Elimination of HP1 alpha by siRNA interfered with centromere relocation from heterochromatin surrounding NPBs to pro-chromocenters at the two-cell stage but did not affect preimplantation develoment to the blastocyst stage.