Histone tyrosine sulfation by SULT1B1 regulates H3R3me2a and gene transcription
Histone tyrosine sulfation by SULT1B1 regulates H3R3me2a and gene transcription
复制标题
SULT1B1 的组蛋白酪氨酸硫酸化调节 H3R3me2a 和基因转录
作者：
Weixing Yu;Runxin Zhou;Nan Li;Zhi-Chao Lei;Dingyuan Guo;Fei Peng;Yan Li;Xue Bai;Shan Feng;Yu Wang;Jie He;Sibi Yin;Xiao Zeng;Leya He;Yuan Gao;Mingchang Li;Yusong R Guo;Ke Liu;Yugang Wang
酪氨酸硫化是哺乳动物中常见的翻译后修饰。到目前为止，它被认为仅限于分泌型和跨膜蛋白，但对核蛋白上的酪氨酸硫化知之甚少。在此，我们报道了SULT1B1是一种组蛋白硫基转移酶，它能在胞浆中硫化新生的组蛋白H3的酪氨酸-99残基。硫酸化的组蛋白H3可以转运到细胞核内，并主要沉积在染色质基因的启动子区域。当H3Y99-残基埋在八聚体核小体内时，动态调节的亚核小体结构为染色质-H3Y99硫磺提供了被PRMT1识别和结合的机会，PRMT1将H4R3me2a沉积在染色质中。H3Y99sulf的破坏降低了PRMT1与染色质的结合、H4R3me2a水平和基因转录。这些发现揭示了H3Y99硫化及其与H4R3me2a的串扰调节基因转录的机制。它扩展了核蛋白上酪氨酸硫化的光谱和调节染色质功能的组蛋白修饰的谱系。
Tyrosine sulfation is a common post-translational 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 sulftransferase that can sulfate the tyrosine-99 residue of nascent histone H3 in cytosol. The sulfated histone H3 can be transported into 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 opportunities 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. It extends the spectrum of tyrosine sulfation on nuclear proteins and the repertoire of histone modifications regulating chromatin functions.