A novel histone H4 variant H4G regulates rDNA transcription in breast cancer

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 H...

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Bibliographic Details
Published in:Nucleic acids research 2019-09, Vol.47 (16), p.8399-8409
Main Authors: Long, Mengping, Sun, Xulun, Shi, Wenjin, Yanru, An, Leung, Sophia T C, Ding, Dongbo, Cheema, Manjinder S, MacPherson, Nicol, Nelson, Christopher J, Ausio, Juan, Yan, Yan, Ishibashi, Toyotaka
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Binding Sites
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Cycle - genetics
Cell Line, Tumor
Cell Nucleolus - genetics
Cell Nucleolus - metabolism
DNA, Ribosomal - chemistry
DNA, Ribosomal - genetics
DNA, Ribosomal - metabolism
Female
Gene Expression Regulation, Neoplastic
Gene regulation, Chromatin and Epigenetics
Gorilla gorilla
Histones - chemistry
Histones - genetics
Histones - metabolism
Humans
Mice
Mice, Knockout
Neoplasm Staging
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Pan troglodytes
Protein Binding
Protein Isoforms - chemistry
Protein Isoforms - genetics
Protein Isoforms - metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Transcription, Genetic
Tumor Burden
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkz547