SHP‐1 dephosphorylates histone H2B to facilitate its ubiquitination during transcription. (8th August 2022)

• Record Type: Journal Article
• Authors: Tathe, Prajakta; Chowdary, K V S Rammohan; Murmu, Krushna Chandra; Prasad, Punit; Maddika, Subbareddy
• Is Part Of: EMBO journal. Volume 41:Number 19(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-08
• Subjects: H2B ubiquitination -- histone H2B -- Paf1 complex -- SHP‐1 -- transcription; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021109720
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: 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. Synopsis: Reversible histone phosphorylation is known to play a critical role during transcription. In this study, a new histone modification –H2B Y121 phosphorylation– controlled by a phosphatase SHP‐1, is shown to mediate a functional crosstalk with H2B ubiquitination during transcription. Tyrosine phosphatase SHP‐1 interacts with the Paf1 complex and histones Nuclear SHP‐1 dephosphorylates histone H2B at Y121 residue Loss of SHP‐1 leads to alteration in genome‐wide H2B ubiquitination and RNA Pol II occupancy Crosstalk between Y121 dephosphorylation and H2B ubiquitination contributes to for productive transcription Abstract : The tyrosine phosphatase SHP‐1 dephosphorylates H2B and interacts with the Paf1 complex to promote transcription.