Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Nat Chem Biol. 2023 Jul;19(7):855-864. doi: 10.1038/s41589-023-01267-9. Epub 2023 Feb 20.
Tyrosine sulfation is a common posttranslational modification in mammals. To date, it has been thought to be limited to secreted and transmembrane proteins, but little is known about tyrosine sulfation on nuclear proteins. Here we report that SULT1B1 is a histone sulfotransferase that can sulfate the tyrosine 99 residue of nascent histone H3 in cytosol. The sulfated histone H3 can be transported into the nucleus and majorly deposited in the promoter regions of genes in chromatin. While the H3Y99 residue is buried inside octameric nucleosome, dynamically regulated subnucleosomal structures provide chromatin-H3Y99sulf the opportunity of being recognized and bound by PRMT1, which deposits H4R3me2a in chromatin. Disruption of H3Y99sulf reduces PRMT1 binding to chromatin, H4R3me2a level and gene transcription. These findings reveal the mechanisms underlying H3Y99 sulfation and its cross-talk with H4R3me2a to regulate gene transcription. This study extends the spectrum of tyrosine sulfation on nuclear proteins and the repertoire of histone modifications regulating chromatin functions.
酪氨酸硫酸化是哺乳动物中一种常见的翻译后修饰。迄今为止，人们认为它仅限于分泌蛋白和跨膜蛋白，但对核蛋白中的酪氨酸硫酸化知之甚少。在这里，我们报告 SULT1B1 是一种组蛋白硫酸转移酶，它可以使细胞质中新生组蛋白 H3 的酪氨酸 99 残基硫酸化。硫酸化的组蛋白 H3 可以被运送到细胞核，并主要沉积在染色质中基因的启动子区域。虽然 H3Y99 残基埋藏在八聚体核小体内部，但动态调节的亚核小体结构为 PRMT1 提供了识别和结合染色质-H3Y99sulf 的机会，PRMT1 将 H4R3me2a 沉积在染色质中。破坏 H3Y99sulf 会减少 PRMT1 与染色质的结合、H4R3me2a 水平和基因转录。这些发现揭示了 H3Y99 硫酸化及其与 H4R3me2a 相互作用调节基因转录的机制。本研究扩展了核蛋白上酪氨酸硫酸化的范围以及调节染色质功能的组蛋白修饰谱。
