The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains.
The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains.
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DOI：
10.1371/journal.pgen.1000726
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发表时间：
2009-11
期刊：
影响因子：
4.5
通讯作者：
Francis Stewart A
中科院分区：
文献类型：
--
作者：
Buchanan L;Durand-Dubief M;Roguev A;Sakalar C;Wilhelm B;Strålfors A;Shevchenko A;Aasland R;Shevchenko A;Ekwall K;Francis Stewart A
真核生物基因组被核小体重复包装成染色质，但核小体之间的差异对其进行调控，从而建立不同的染色质状态。局部染色质信号通过自我强化的表观遗传机制指导染色质状态的遗传和传播。如果组蛋白交换伴侣蛋白，如Swr1C，将组蛋白变体加载到错误的位置，复制无关的组蛋白交换可能潜在地扰乱染色质的状态。在这里，我们证明了在裂殖酵母中，像酿酒酵母一样，Swr1C是将H2A.Z装载到特定位置所必需的，包括低表达基因的启动子。然而，S.pombe Swr1C有一个额外的亚基Msc1，它是LID/Jarid1家族的JumonjiC结构域蛋白。Msc1的缺失不会破坏S.pombe Swr1C与常染色质结合和装载H_2A.Z的能力，但H_2A.Z异位存在于着丝粒内侧和亚端粒染色质中。正常情况下，这一亚端粒区域不仅缺乏H2A.Z，而且H3K4me2、H4K5和K12乙酰化水平一致低于常染色质，并且不成比例地包含营养生长过程中表达最低的基因，包括许多减数分裂特异基因。在没有Msc1、Swr1或矛盾的是H_2A.Z本身的情况下，亚端粒染色质内及其邻近的基因会过度表达。我们还表明，H2A.Z在装载到染色质之前是N-末端乙酰化的，赖氨酸在装载到染色质后是乙酰化的，并且它物理上与NAP1组蛋白伴侣结合。然而，我们发现H_2A.Z的基因组分布与NAP1/Hrp1/Hrp3呈负相关，表明NAP1伴侣蛋白从染色质中去除H_2A.Z。这些数据描述了H2A.Z在S.pombe中的作用，并确定了一种基于组蛋白变体误结合的负调控的染色质监测和维持的新模式。染色质是基于一种称为核小体的重复结构单位。然而，染色质的调节特性是由核小体之间的差异介导的，这是由于翻译后修饰或包含组蛋白变体。这些差异是通过顺式作用的表观遗传机制保持的。在这里，我们描述了一个情况，染色质的局部特性不仅由顺式作用机制决定，而且在反式作用中也受到负调控。该案涉及将组蛋白H_2A变异体H_2A_Z加载到染色质中。我们发现酵母裂殖酵母中的H2A.Z主要存在于第一个转录的核小体的基因中，并通过Swr1C重塑机器插入到这个核小体中。然而，Swr1C有一个调节亚单位Msc1，它不是H2A.Z启动子装载所必需的，但它阻止了H2A.Z在内部着丝粒和亚端粒区域的占据。这两个专化区既不是欧盟-也不是异染色质，具有某些共同的特征，这可能使它们易于异常地包含H2A.Z和需要Msc1的反式调控。
Eukaryotic genomes are repetitively packaged into chromatin by nucleosomes, however they are regulated by the differences between nucleosomes, which establish various chromatin states. Local chromatin cues direct the inheritance and propagation of chromatin status via self-reinforcing epigenetic mechanisms. Replication-independent histone exchange could potentially perturb chromatin status if histone exchange chaperones, such as Swr1C, loaded histone variants into wrong sites. Here we show that in Schizosaccharomyces pombe, like Saccharomyces cerevisiae, Swr1C is required for loading H2A.Z into specific sites, including the promoters of lowly expressed genes. However S. pombe Swr1C has an extra subunit, Msc1, which is a JumonjiC-domain protein of the Lid/Jarid1 family. Deletion of Msc1 did not disrupt the S. pombe Swr1C or its ability to bind and load H2A.Z into euchromatin, however H2A.Z was ectopically found in the inner centromere and in subtelomeric chromatin. Normally this subtelomeric region not only lacks H2A.Z but also shows uniformly lower levels of H3K4me2, H4K5, and K12 acetylation than euchromatin and disproportionately contains the most lowly expressed genes during vegetative growth, including many meiotic-specific genes. Genes within and adjacent to subtelomeric chromatin become overexpressed in the absence of either Msc1, Swr1, or paradoxically H2A.Z itself. We also show that H2A.Z is N-terminally acetylated before, and lysine acetylated after, loading into chromatin and that it physically associates with the Nap1 histone chaperone. However, we find a negative correlation between the genomic distributions of H2A.Z and Nap1/Hrp1/Hrp3, suggesting that the Nap1 chaperones remove H2A.Z from chromatin. These data describe H2A.Z action in S. pombe and identify a new mode of chromatin surveillance and maintenance based on negative regulation of histone variant misincorporation. Chromatin is based on a repetitive structural unit called the nucleosome. However, the regulatory properties of chromatin are mediated by the differences between nucleosomes, due to post-translational modifications or the inclusion of histone variants. These differences are maintained by inheritance through cis-acting epigenetic mechanisms. Here we describe a case where the local character of chromatin is not only determined by cis-acting mechanisms but also negatively regulated in trans. The case involves loading of the histone H2A variant, H2A.Z, into chromatin. We show that H2A.Z in the yeast Schizosaccharomyces pombe is mainly found in genes at the first transcribed nucleosome and is inserted into this nucleosome by the Swr1C remodeling machine. However, Swr1C has a regulatory subunit, Msc1, which is not required for H2A.Z promoter loading but prevents H2A.Z occupancy in the inner centromere and subtelomeric regions. These two specialized regions are neither eu- nor heterochromatin and share certain characteristics, which may predispose them to the aberrant inclusion of H2A.Z and the requirement for trans regulation by Msc1.
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影响因子：
5.3
作者：
Ahmed, S;Palermo, C;Walworth, NC
通讯作者：
Walworth, NC
DOI：
10.1073/pnas.172403699
发表时间：
2002-12-10
影响因子：
11.1
作者：
Ahmad, K;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
4.8
作者：
Dul, Barbara E.;Walworth, Nancy C.
通讯作者：
Walworth, Nancy C.
DOI：
10.1007/bf00282226
发表时间：
1994-12-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
CARR, AM;DORRINGTON, SM;NURSE, P
通讯作者：
NURSE, P
影响因子：
16
作者：
Bushey, Ashley M.;Dorman, Elizabeth R.;Corces, Victor G.
通讯作者：
Corces, Victor G.