TY - JOUR
T1 - Nuclear myosin 1 activates p21 gene transcription in response to DNA damage through a chromatin-based mechanism
AU - Venit, Tomas
AU - Semesta, Khairunnisa
AU - Farrukh, Sannia
AU - Endara-Coll, Martin
AU - Havalda, Robert
AU - Hozak, Pavel
AU - Percipalle, Piergiorgio
N1 - Funding Information:
This work is primarily supported by grants from New York University Abu Dhabi, the Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences, the Swedish Research Council (Vetenskapsrådet), and the Swedish Cancer Society (Cancerfonden) to P.P. We thank the NYU Abu Dhabi Center for Genomics and Systems Biology, in particular Marc Arnoux and Mehar Sultana for technical help, as well as Core Technology Platform Resources, including the NYU Abu Dhabi imaging center. We appreciate the computational platform provided by NYUAD HPC team and are especially thankful to Yousif Ayman and Nizar Drou for technical help. The study was also supported by the Grant Agency of the Czech Republic (17–09103s, 16–03346s, and 15–08738s). We acknowledge the Microscopy Centre–Light/Electron CF, IMG AS CR supported by the Czech-BioImaging large RI project (LM2015062 funded by MEYS CR) for technical help. The results achieved with institutional support were obtained with the support of long-term conceptual development of the scientific organization (RVO: 68378050). This publication is also supported by the project “BIOCEV–Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” (CZ.1.05/ 1.1.00/02.0109), from the European Regional Development Fund.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Together with actin, it has been shown to initiate and regulate transcription, it is part of the chromatin remodeling complex B-WICH, and is responsible for rearrangements of chromosomal territories in response to external stimuli. Here we show that deletion of NM1 in mouse embryonic fibroblasts leads to chromatin and transcription dysregulation affecting the expression of DNA damage and cell cycle genes. NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation. We propose a role for NM1 in the transcriptional response to DNA damage response and maintenance of genome stability.
AB - Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Together with actin, it has been shown to initiate and regulate transcription, it is part of the chromatin remodeling complex B-WICH, and is responsible for rearrangements of chromosomal territories in response to external stimuli. Here we show that deletion of NM1 in mouse embryonic fibroblasts leads to chromatin and transcription dysregulation affecting the expression of DNA damage and cell cycle genes. NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation. We propose a role for NM1 in the transcriptional response to DNA damage response and maintenance of genome stability.
UR - http://www.scopus.com/inward/record.url?scp=85081745491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081745491&partnerID=8YFLogxK
U2 - 10.1038/s42003-020-0836-1
DO - 10.1038/s42003-020-0836-1
M3 - Article
C2 - 32161327
AN - SCOPUS:85081745491
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 115
ER -