Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation.
Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation.
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DOI：
10.1093/nar/gkaa1093
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发表时间：
2020-12-02
影响因子：
14.9
通讯作者：
Hochstrasser M
中科院分区：
文献类型：
--
作者：
Ryu HY;Zhao D;Li J;Su D;Hochstrasser M
组蛋白是SUMO（小泛素样修饰物）缀合途径的底物。一些报道表明组蛋白类小泛素化对转录有负面影响，但矛盾的是，我们的全基因组分析显示，这种修饰集中在许多活性基因上。我们发现组蛋白H2B泛素化和H3K4去甲基化的反尾调节增强了随后的组蛋白SUMO化。与已知的H3K4去甲基化对Set3组蛋白脱乙酰酶复合物（HDAC）的控制一致，组蛋白SUMO化通过HDAC Cpr1亚基中的SUMO相互作用基序直接将Set3复合物募集到蛋白质编码和非编码RNA（ncRNA）基因。由减少组蛋白类小泛素化引起的基因表达谱的改变与缺乏Set3的细胞中的基因表达谱很好地匹配。组蛋白H2B类小泛素化和Set3 HDAC协同抑制mRNA基因内部的隐蔽ncRNA转录起始。我们的研究结果揭示了一个复杂的共转录组蛋白串扰途径，涉及组蛋白的连续泛素化，甲基化，sumo化和脱乙酰化，通过抑制假转录来保持转录的保真度。
Histones are substrates of the SUMO (small ubiquitin-like modifier) conjugation pathway. Several reports suggest histone sumoylation affects transcription negatively, but paradoxically, our genome-wide analysis shows the modification concentrated at many active genes. We find that trans-tail regulation of histone-H2B ubiquitylation and H3K4 di-methylation potentiates subsequent histone sumoylation. Consistent with the known control of the Set3 histone deacetylase complex (HDAC) by H3K4 di-methylation, histone sumoylation directly recruits the Set3 complex to both protein-coding and noncoding RNA (ncRNA) genes via a SUMO-interacting motif in the HDAC Cpr1 subunit. The altered gene expression profile caused by reducing histone sumoylation matches well to the profile in cells lacking Set3. Histone H2B sumoylation and the Set3 HDAC coordinately suppress cryptic ncRNA transcription initiation internal to mRNA genes. Our results reveal an elaborate co-transcriptional histone crosstalk pathway involving the consecutive ubiquitylation, methylation, sumoylation and deacetylation of histones, which maintains transcriptional fidelity by suppressing spurious transcription.
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