RT Journal Article
SR Electronic
T1 Histone chaperone Nucleophosmin regulates transcription of key genes involved in oral tumorigenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 852095
DO 10.1101/852095
A1 Parijat Senapati
A1 Suchismita Dey
A1 Deepthi Sudarshan
A1 Aditya Bhattacharya
A1 Shyla G
A1 Sadhan Das
A1 Surabhi Sudevan
A1 Tessy Thomas Maliekal
A1 Tapas K. Kundu
YR 2019
UL http://biorxiv.org/content/early/2019/11/22/852095.abstract
AB Nucleophosmin (NPM1) is a multifunctional histone chaperone that can activate RNA Polymerase II-driven chromatin transcription. Acetylation of NPM1 by acetyltransferase p300 has been shown to further enhance its transcription activation potential. Moreover, its total and acetylated pools are increased in oral squamous cell carcinoma. However, the role of NPM1 or its acetylated form (AcNPM1) in transcriptional regulation in cells is not fully elucidated. Using ChIP-seq analyses, we show that AcNPM1 co-occupies marks of active transcription at promoters and DNase I hypersensitive sites at enhancers. Moreover, NPM1 interacts with proteins involved in transcription, including RNA Pol II, general transcription factors, mediator subunits, histone acetyltransferase complexes, and chromatin remodelers. Moreover, its histone chaperone also contributes to transcriptional activation. We further show that AcNPM1 regulates key genes required for proliferation, migration and invasion potential of oral cancer cells and knockdown of NPM1 mitigates these processes in cells as well as orthotopic tumors in mice. Collectively, these results establish that AcNPM1 functions as a coactivator and regulates the expression of key genes involved in oral tumorigenesis.