Histone H4 variant, H4G, drives ribosomal RNA transcription and breast cancer cell proliferation by loosening nucleolar chromatin structure

The hominidae‐specific histone variant H4G is expressed in breast cancer patients in a stage‐dependent manner. H4G localizes primarily in the nucleoli via its interaction with nucleophosmin (NPM1). H4G is involved in rDNA transcription and ribosome biogenesis, which facilitates breast cancer cell pr...

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Bibliographic Details
Published in:Journal of cellular physiology 2020-12, Vol.235 (12), p.9601-9608
Main Authors: Pang, Matthew Y. H., Sun, Xulun, Ausió, Juan, Ishibashi, Toyotaka
Format: Article
Language:English
Subjects:
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell growth
Cell Line, Tumor
Cell Nucleolus - genetics
Cell Nucleolus - ultrastructure
Cell proliferation
Cell Proliferation - genetics
Chromatin
Chromatin - genetics
Chromatin - ultrastructure
Female
Gene Expression Regulation, Neoplastic - genetics
Genetic Variation - genetics
Histone H4
histone H4G
histone variant
Histones
Histones - genetics
Humans
Loosening
NPM1
Nuclear Proteins - genetics
Nucleoli
Nucleosomes - genetics
Nucleosomes - ultrastructure
rDNA transcription
RNA, Ribosomal - genetics
rRNA
Transcription
Transcription, Genetic
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Summary:The hominidae‐specific histone variant H4G is expressed in breast cancer patients in a stage‐dependent manner. H4G localizes primarily in the nucleoli via its interaction with nucleophosmin (NPM1). H4G is involved in rDNA transcription and ribosome biogenesis, which facilitates breast cancer cell proliferation. However, the molecular mechanism underlying this process remains unknown. Here, we show that H4G is not stably incorporated into nucleolar chromatin, even with the chaperoning assistance of NPM1. H4G likely form transient nucleosome‐like‐structure that undergoes rapid dissociation. In addition, the nucleolar chromatin in H4GKO cells is more compact than WT cells. Altogether, our results suggest that H4G relaxes the nucleolar chromatin and enhances rRNA transcription by forming destabilized nucleosome in breast cancer cells. The hominidae‐specific histone variant H4G likely forms transient nucleosome‐like‐structure that undergoes rapid dissociation. Our results suggest that H4G relaxes the nucleolar chromatin and enhances rRNA transcription by forming destabilized nucleosome in breast cancer cells.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.29770