The eukaryotic genomic DNA is compacted by assembling into nucleosome core particles. Histone variants are substitutes for the canonical histones in nucleosomes, which usually possess alternative chromatin structural patterns and serve as the additional layer of epigenetic processes.

H4G is the only histone H4 variant found in the human genome. As a hominidae-specific gene, it is present in chromosome 6 within the histone cluster 1, where many histone genes are located. H4G shares only 85% amino acid sequence identity with the canonical H4. I found that H4G is expressed especially in breast cancer cell lines and breast cancer tissues in a tumor-stage dependent manner. It primarily localizes to the nucleoli of the cell and its endogenous protein expression has been confirmed by...[ Read more ]

The eukaryotic genomic DNA is compacted by assembling into nucleosome core particles. Histone variants are substitutes for the canonical histones in nucleosomes, which usually possess alternative chromatin structural patterns and serve as the additional layer of epigenetic processes.

H4G is the only histone H4 variant found in the human genome. As a hominidae-specific gene, it is present in chromosome 6 within the histone cluster 1, where many histone genes are located. H4G shares only 85% amino acid sequence identity with the canonical H4. I found that H4G is expressed especially in breast cancer cell lines and breast cancer tissues in a tumor-stage dependent manner. It primarily localizes to the nucleoli of the cell and its endogenous protein expression has been confirmed by mass spectrometry. Furthermore, biochemical experiments showed that the nucleolar localization of H4G is mediated by the interaction of its α-helix 3 histone fold domain and a multifunctional histone chaperone nucleophosmin 1 (NPM1). Functional analysis indicated that H4G promotes rRNA transcription, protein synthesis and breast cancer cell proliferation. However, based on in vitro and in vivo studies, H4G is not incorporated into the nucleolar chromatin even with the chaperoning assistance of NPM1. Instead, H4G may interfere with the histone chaperone activity of NPM1 and alter the nucleolar chromatin configuration. Taken together, these results suggest that H4G expression alters nucleolar chromatin and enhances rRNA transcription in breast cancer cells.