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TOX4 Promotes Promoter Proximal Pause of RNA Polymerase Ii by Facilitating the Recruitment of DSIF and NELF

Authors :
Ziling Liu
Talang Wang
Zhen Wu
Ming Yu
Aiwei Wu
Xumin Zhang
Source :
SSRN Electronic Journal.
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Protein phosphatase 1 complex (PP1C), consisting of one of the phosphatases, PP1α, β and γ, and three regulatory subunits, PNUTS, TOX4 and WDR82, plays critical roles in gene regulation and is mutated in over 20% of uterine corpus endometrial carcinoma cases. TOX4 is the least understood PP1C subunit. Here we show that chromatin occupancy pattern of TOX4 resembles that of RNA polymerase II (Pol II), and its loss increases the phosphorylation of the C-terminal domain and decreases the global occupancy of Pol II. Mechanistically, it promotes promoter-proximal pause of Pol II by facilitating the recruitment of DSIF and NELF likely in a dephosphorylation dependent manner. Moreover, quantitative proteomic analyses revealed that TOX4 mainly facilitates protein dephosphorylation by PP1 phosphatases. Furthermore, Tox4 knockout in mice impairs T cell development by dysregulating genes critical for survival, proliferation and fate determination. These results lay the foundation for further understanding roles of TOX4 in transcription, development and diseases.

Details

ISSN :
15565068
Database :
OpenAIRE
Journal :
SSRN Electronic Journal
Accession number :
edsair.doi...........a2b1f0da6ca88785dedb40e1b55a3232
Full Text :
https://doi.org/10.2139/ssrn.3823429