Histone variants are non-allelic variants of core canonical histones which have different amino acid sequences. Numerous studies have showed their diverse roles in chromatin regulation. The most studied histone variants are those of H3 and H2A. Compared to H1, H2A, H2B and H3, histone H4 is currently the only one without histone variants.

In this study, we characterized H4G, a novel hominid-specific histone H4 variant. The mRNA expression of H4G was found in various human cell lines. It was also overexpressed in human breast carcinoma tissues compared to normal breast tissue with its expression positively correlated with the cancer TNM stage and most prominent in Luminal type. H4G was found to localize primarily to the nucleolus. This localization was controlled by the interacti...[ Read more ]

Histone variants are non-allelic variants of core canonical histones which have different amino acid sequences. Numerous studies have showed their diverse roles in chromatin regulation. The most studied histone variants are those of H3 and H2A. Compared to H1, H2A, H2B and H3, histone H4 is currently the only one without histone variants.

In this study, we characterized H4G, a novel hominid-specific histone H4 variant. The mRNA expression of H4G was found in various human cell lines. It was also overexpressed in human breast carcinoma tissues compared to normal breast tissue with its expression positively correlated with the cancer TNM stage and most prominent in Luminal type. H4G was found to localize primarily to the nucleolus. This localization was controlled by the interaction of the α helix 3 of the histone fold motif with the histone chaperone, Nucleophosmin 1 (NPM1). In addition, we found that H4G nucleolar localization increased rRNA levels, protein synthesis rates, and cell cycle progression. Knockout of H4G in MCF-7 would also decrease cell growth rate in mouse xenograft model. Furthermore, micrococcal nuclease digestion and salt stability analysis of H4G-containing nucleosomes reconstituted in vitro indicated that H4G destabilizes the nucleosome, which may serve to alter nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues. Last, in the mitosis phase, H4G also localizes at centrosome with its function still need to be revealed.