School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of National Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
Yale Center for Genome Analysis, Yale University, New Haven, CT 06520, USA.
Nucleic Acids Res. 2020 Dec 2;48(21):12151-12168. doi: 10.1093/nar/gkaa1093.
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.
组蛋白是 SUMO（小泛素样修饰物）缀合途径的底物。有几项报告表明组蛋白 SUMO 化会负向影响转录，但矛盾的是，我们的全基因组分析表明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 二甲基化的反式尾巴调控增强了随后的组蛋白 SUMO 化。与 Set3 组蛋白去乙酰化酶复合物（HDAC）由 H3K4 二甲基化控制的已知情况一致，组蛋白 SUMO 化通过 HDAC Cpr1 亚基中的 SUMO 相互作用基序直接将 Set3 复合物招募到蛋白质编码和非编码 RNA（ncRNA）基因上。降低组蛋白 SUMO 化引起的基因表达谱与缺乏 Set3 的细胞中的表达谱非常匹配。组蛋白 H2B SUMO 化和 Set3 HDAC 协同抑制 mRNA 基因内的隐蔽 ncRNA 转录起始。我们的结果揭示了一种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 化和去乙酰化，通过抑制虚假转录来维持转录保真度。
