Cell cycle control of centromeric repeat transcription and heterochromatin assembly
Cell cycle control of centromeric repeat transcription and heterochromatin assembly
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DOI：
10.1038/nature06561
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发表时间：
2008-02-07
期刊：
影响因子：
64.8
通讯作者：
Grewal, Shiv I. S.
中科院分区：
文献类型：
--
作者：
Chen, Ee Sin;Zhang, Ke;Grewal, Shiv I. S.
真核生物基因组中的异染色质调节包括转录沉默在内的多种染色体过程(1)。然而，在Schizosaccharomyces pombe RNA聚合酶II （RNAPII）中，着丝粒重复序列的转录对于RNA干扰介导的异染色质组装是必不可少的（2-5）。在这里，我们研究细胞周期中的异染色质动力学及其对RNAPII转录的影响。我们描述了在细胞周期S期的一个短暂时期，RNAPII优先转录着丝粒重复序列。这一时期是由异染色质强制的，在大多数细胞周期中，它限制了RNAPII在着丝点重复处的可及性。S期RNAPII的转录与RNA干扰和异染色质因子(如RITS复合体的Ago1亚基（6)和Clr4甲基转移酶复合体亚基Rik1（参考文献7））的负载有关。此外，Set2，一种RNAPII相关的甲基转移酶(8)，在S期重复位点甲基化组蛋白H3赖氨酸36，在与Clr4平行的途径中促进异染色质组装。我们还发现，在有丝分裂过程中，组蛋白H3丝氨酸10的磷酸化改变了异染色质，与凝缩蛋白的募集相关，凝缩蛋白的募集影响着着丝粒重复序列的沉默。我们的分析表明，至少有两种不同的异染色质靶向着丝点重复序列的模式，其中重复序列的RNAPII转录和与甲基化组蛋白H3赖氨酸9结合的色域蛋白介导沉默因子的募集。总之，这些过程可能通过连续的细胞分裂促进异染色质的维持。
Heterochromatin in eukaryotic genomes regulates diverse chromosomal processes including transcriptional silencing(1). However, in Schizosaccharomyces pombe RNA polymerase II ( RNAPII) transcription of centromeric repeats is essential for RNA- interference- mediated heterochromatin assembly(2-5). Here we study heterochromatin dynamics during the cell cycle and its effect on RNAPII transcription. We describe a brief period during the S phase of the cell cycle in which RNAPII preferentially transcribes centromeric repeats. This period is enforced by heterochromatin, which restricts RNAPII accessibility at centromeric repeats for most of the cell cycle. RNAPII transcription during S phase is linked to loading of RNA interference and heterochromatin factors such as the Ago1 subunit of the RITS complex(6) and the Clr4 methyltransferase complex subunit Rik1 ( ref. 7). Moreover, Set2, an RNAPII- associated methyltransferase(8) that methylates histone H3 lysine 36 at repeat loci during S phase, acts in a pathway parallel to Clr4 to promote heterochromatin assembly. We also show that phosphorylation of histone H3 serine 10 alters heterochromatin during mitosis, correlating with recruitment of condensin that affects silencing of centromeric repeats. Our analyses suggest at least two distinct modes of heterochromatin targeting to centromeric repeats, whereby RNAPII transcription of repeats and chromodomain proteins bound to methylated histone H3 lysine 9 mediate recruitment of silencing factors. Together, these processes probably facilitate heterochromatin maintenance through successive cell divisions.