The Chaperone FACT and Histone H2B Ubiquitination Maintain S. pombe Genome Architecture through Genic and Subtelomeric Functions.
The Chaperone FACT and Histone H2B Ubiquitination Maintain S. pombe Genome Architecture through Genic and Subtelomeric Functions.
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DOI：
10.1016/j.molcel.2019.11.016
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发表时间：
2019-12
期刊：
影响因子：
16
通讯作者：
M. Murawska;Tamás Schauer;A. Matsuda;M. D. Wilson;Thomas Pysik;Felix Wojcik;T. Muir;Y. Hiraoka;T. Straub;A. Ladurner
中科院分区：
文献类型：
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作者：
M. Murawska;Tamás Schauer;A. Matsuda;M. D. Wilson;Thomas Pysik;Felix Wojcik;T. Muir;Y. Hiraoka;T. Straub;A. Ladurner
组蛋白伴侣蛋白FACT和组蛋白H2B泛素化（H2Bub）促进RNA聚合酶II（Pol II）通过染色质，但尚不清楚它们如何在机制上合作。我们使用基因组学，遗传，生物化学和显微镜的方法来解剖它们的相互作用inSchizoschiomaceuspombe。我们发现FACT和H2Bub分别在基因5′端和基因体内全面抑制反义转录物。这些转录本的积累伴随着基因核小体和Pol II再分布的变化。H2Bub是基因区域中FACT活性所必需的。在H2Bub突变体中，FACT与染色质的结合被改变，其与组蛋白的结合被稳定，这导致基因核小体的减少。有趣的是，FACT耗竭在H2Bub突变体中全面恢复核小体。此外，在缺乏Pob3的情况下，FACT Spt16亚基控制基因的3′端。此外，FACT在亚端粒区域维持核小体，这对于它们的压实至关重要。
The histone chaperone FACT and histone H2B ubiquitination (H2Bub) facilitate RNA polymerase II (Pol II) passage through chromatin, yet it is not clear how they cooperate mechanistically. We used genomics, genetic, biochemical, and microscopic approaches to dissect their interplay inSchizosaccharomyces pombe. We show that FACT and H2Bub globally repress antisense transcripts near the 5′ end of genes and inside gene bodies, respectively. The accumulation of these transcripts is accompanied by changes at genic nucleosomes and Pol II redistribution. H2Bub is required for FACT activity in genic regions. In the H2Bub mutant, FACT binding to chromatin is altered and its association with histones is stabilized, which leads to the reduction of genic nucleosomes. Interestingly, FACT depletion globally restores nucleosomes in the H2Bub mutant. Moreover, in the absence of Pob3, the FACT Spt16 subunit controls the 3′ end of genes. Furthermore, FACT maintains nucleosomes in subtelomeric regions, which is crucial for their compaction.