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SHP-1 dephosphorylates histone H2B to facilitate its ubiquitination during transcription
The EMBO Journal ( IF 9.4 ) Pub Date : 2022-08-08 , DOI: 10.15252/embj.2021109720
Prajakta Tathe 1, 2 , K V S Rammohan Chowdary 1 , Krushna Chandra Murmu 3 , Punit Prasad 3 , Subbareddy Maddika 1
Affiliation  

Dynamic regulation of phosphorylation and dephosphorylation of histones is essential for eukaryotic transcription, but the enzymes engaged in histone dephosphorylation are not fully explored. Here, we show that the tyrosine phosphatase SHP-1 dephosphorylates histone H2B and plays a critical role during transition from the initiation to the elongation stage of transcription. Nuclear-localized SHP-1 is associated with the Paf1 complex at chromatin and dephosphorylates H2B at tyrosine 121. Moreover, knockout of SHP-1, or expression of a mutant mimicking constitutive phosphorylation of H2B Y121, leads to a reduction in genome-wide H2B ubiquitination, which subsequently causes defects in RNA polymerase II-dependent transcription. Mechanistically, we demonstrate that Y121 phosphorylation precludes H2B's interaction with the E2 enzyme, indicating that SHP-1-mediated dephosphorylation of this residue may be a prerequisite for efficient H2B ubiquitination. Functionally, we find that SHP-1-mediated H2B dephosphorylation contributes to maintaining basal autophagic flux in cells through the efficient transcription of autophagy and lysosomal genes. Collectively, our study reveals an important modification of histone H2B regulated by SHP-1 that has a role during eukaryotic transcription.

中文翻译:

SHP-1 使组蛋白 H2B 去磷酸化,以促进其在转录过程中泛素化

组蛋白磷酸化和去磷酸化的动态调节对于真核转录至关重要,但参与组蛋白去磷酸化的酶尚未得到充分探索。在这里,我们发现酪氨酸磷酸酶 SHP-1 使组蛋白 H2B 去磷酸化,并在转录起始阶段到延伸阶段的过渡过程中发挥关键作用。核定位的 SHP-1 与染色质处的 Paf1 复合物相关,并在酪氨酸 121 处使 H2B 去磷酸化。此外,SHP-1 的敲除或模拟 H2B Y121 组成型磷酸化的突变体的表达会导致全基因组 H2B 的减少泛素化,随后导致 RNA 聚合酶 II 依赖性转录缺陷。从机制上讲,我们证明 Y121 磷酸化阻止了 H2B 与 E2 酶的相互作用,表明 SHP-1 介导的该残基的去磷酸化可能是有效 H2B 泛素化的先决条件。从功能上讲,我们发现 SHP-1 介导的 H2B 去磷酸化有助于通过自噬和溶酶体基因的有效转录维持细胞中的基础自噬通量。总的来说,我们的研究揭示了 SHP-1 调节的组蛋白 H2B 的一个重要修饰,该修饰在真核转录过程中发挥作用。
更新日期:2022-08-08
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