Open AccessA novel histone H4 variant H4G regulates rDNA transcription in breast cancer
Author(s) -
Mengping Long,
Xulun Sun,
Weimin Shi,
Yanru An,
S. S. F. Leung,
Dongbo Ding,
Manjinder S. Cheema,
Nicol Macpherson,
Christopher J. Nelson,
Juan Ausió,
Yan Yan,
Toyotaka Ishibashi
Publication year - 2019
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkz547
Subject(s) - biology , chromatin , nucleolus , histone , histone h2a , histone h4 , histone h1 , sap30 , microbiology and biotechnology , histone code , cancer research , genetics , gene , nucleosome , nucleus
Histone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.