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Histone H4 variant, H4G, drives ribosomal RNA transcription and breast cancer cell proliferation by loosening nucleolar chromatin structure
Author(s) -
Pang Matthew Y. H.,
Sun Xulun,
Ausió Juan,
Ishibashi Toyotaka
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29770
Subject(s) - nucleolus , chromatin , ribosome biogenesis , nucleophosmin , microbiology and biotechnology , nucleosome , biology , transcription (linguistics) , histone , cancer research , chromatin remodeling , rna , ribosome , genetics , dna , gene , linguistics , philosophy , myeloid leukemia , cytoplasm
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.