Histone H2B C-Terminal Helix Mediates trans-Histone H3K4 Methylation Independent of H2B Ubiquitination
Histone H2B C-Terminal Helix Mediates trans-Histone H3K4 Methylation Independent of H2B Ubiquitination
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DOI：
10.1128/mcb.01008-09
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Sun, Zu-Wen
中科院分区：
文献类型：
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作者：
Chandrasekharan, Mahesh B.;Huang, Fu;Sun, Zu-Wen
H2BK123泛素化（H2Bub1）与H3K4和H3K79甲基化之间的反式组蛋白调控串话尚不完全清楚。在本研究中，我们报道了H2B c端螺旋上的残基精氨酸119和苏氨酸122在转录和细胞生长中起重要作用，并直接控制H2Bub1和H3K4甲基化。这些残基通过控制染色质结合和去泛素酶的活性来调节H2Bub1的水平。此外，我们发现h2bub1介导的H3K4和-K79甲基化协同调节的解耦，因为这些H2B c端螺旋残基是一个独特表面的一部分，仅影响Set1- compass（与Set1相关的复杂蛋白）介导的H3K4甲基化，而不影响Dot1的功能。重要的是，我们还发现这些残基与Spp1相互作用，并独立于H2Bub1控制Set1-COMPASS的染色质关联、完整性和整体稳定性。因此，我们发现了H2B c端螺旋在反式组蛋白串扰中作为Set1-COMPASS的结合表面的新作用。我们进一步深入研究了反式组蛋白串扰，并提出H2Bub1通过阻止H2A-H2B的排出来稳定核小体，从而保留了Set1-COMPASS在染色质上的“对接位点”，以维持其稳定的染色质关联、复合物稳定性和过程甲基化。
The trans-histone regulatory cross talk between H2BK123 ubiquitination (H2Bub1) and H3K4 and H3K79 methylation is not fully understood. In this study, we report that the residues arginine 119 and threonine 122 in the H2B C-terminal helix are important for transcription and cell growth and play a direct role in controlling H2Bub1 and H3K4 methylation. These residues modulate H2Bub1 levels by controlling the chromatin binding and activities of the deubiquitinases. Furthermore, we find an uncoupling of the H2Bub1-mediated coregulation of both H3K4 and -K79 methylation, as these H2B C-terminal helix residues are part of a distinct surface that affects only Set1-COMPASS (complex proteins associated with Set1)-mediated H3K4 methylation without affecting the functions of Dot1. Importantly, we also find that these residues interact with Spp1 and control the chromatin association, integrity, and overall stability of Set1-COMPASS independent of H2Bub1. Therefore, we have uncovered a novel role for the H2B C-terminal helix in the trans-histone cross talk as a binding surface for Set1-COMPASS. We provide further insight into the trans-histone cross talk and propose that H2Bub1 stabilizes the nucleosome by preventing H2A-H2B eviction and, thereby, retains the "docking site" for Set1-COMPASS on chromatin to maintain its stable chromatin association, complex stability, and processive methylation.