title: Brief Communication: Featured Article: Histone H2A mono-ubiquitination and cellular transformation are inversely related in N-nitrosodiethylamine-induced hepatocellular carcinoma.
abstract: Aberrant changes in histone post-translational modifications are encountered frequently in diseases like cancer. Although histone H3 post-translational modifications have been extensively studied in context of diseases, the functionally important histone H2A PTM H2A119ub (H2Aub) has not gained much attention. In this study, we report that H2Aub markedly decreases in hepatocellular carcinoma. Usp21, a H2A deubiquitinase, is probably responsible for decrease in H2Aub. In addition, the H2Aub levels showed an inverse correlation with H3S10 phosphorylation (H3S10p) and the proliferative state of the cells. Downregulation of H2Aub is also associated with increased expression of growth factor gene lipocalin 2. Interestingly, we show that treatment of cells with histone deacetylase inhibitor trichostatin A results in increase of H2Aub and decrease in H3S10p. Our work for the first time suggests the in vivo association of H3S10p, H4ac, and H2A119ub with cellular transformation.
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Cancer Research Institute, Kharghar, Navi Mumbai, MH 410210, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Cancer Research Institute, Kharghar, Navi Mumbai, MH 410210, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Reddy
authors.affiliation: Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Cancer Research Institute, Kharghar, Navi Mumbai, MH 410210, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Ingle
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Cancer Research Institute, Kharghar, Navi Mumbai, MH 410210, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Khade
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Cancer Research Institute, Kharghar, Navi Mumbai, MH 410210, India sgupta@actrec.gov.in.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000378:metabolism / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000648:ultrastructure; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D054875:Ubiquitination
chemical_list: D000477:Alkylating Agents; D006657:Histones; D004052:Diethylnitrosamine
keywords: Histone post-translational modifications; cancer; deubiquitination; epigenetics; histone deacetylase inhibitor; lipocalin 2