Recent Research Progress

H1 histone family, member 0 (H1F0) is a member of the H1 histone family of nuclear proteins. It has been shown that, H1F0 is expressed by oocytes from the GV stage to the 2-cell embryo stage in mice and human. Some reports have underlined that H1F0’s coding regions encoded 195 amino acids. The yak H1F0 protein had high similarities with other mammalian species. Hui-Ran Niu et al. has shown that H1F0 is thought to be the predominant H1 histone associated with chromatin during oocyte growth, maturation and early embryogenesis. Keiko Ichihara-Tanaka et al. shows that the accumulation of H1f0 is related to the development of brain tissue. For example, the accumulation of H1f0 coincides with the terminal differentiation of the brain cortex. Furthermore, total expression level of H1f0 gradually decreased from E12.5 to adulthood in brain tissues.

Some researches proved that H1F0 silencing occurs specifically in cancer stem cells (CSCs). Histone H1F0 accumulation has been associated with terminal differentiation in normal cells, while it downgrades in neoplastic cells and different cancer types. At a molecular level, H1F0 showed a mutually exclusive relationship with SSEA1, which is stem cell surface marker Stage Specific Embryonic Antigen 1. At protein level, down-regulation of H1F0 could either decrease the total H1:core histone ratio or instead H1F0 loss could be compensated by an increase of other H1 subtypes.

According to related research, the knockdown of H1F0 in human embryonic stem cells (ESCs) in vitro impaired the induction of genes associated with differentiation (HNF4, Sox17 and FoxA2), suggesting a potential role of H1F0 in regulating specific genes during human ESC differentiation. In addition, H1F0 was enriched at nucleolar-associated domains, rDNA and certain repeats In T47D. Moreover, the analysis of transcriptional data showed that the genes up-regulated upon H1F0 knockdown were associated with oncogene activation and tumor-suppressor inactivation. Therefore, Torres concluded that cells lacking H1F0 undergo genome wide changes in gene expression, triggered by alterations in the nucleosome occupancy around the TSS of genes in AT-rich domains, which led to the up-regulation of genes associated with cancer-cell self-renewal ability. Mechanistically, H1F0 depletion destabilizes nucleosome DNA interactions to promote the expression of self-renewal genes. Gene expression changes following H1F0 loss were reversible and epigenetic states restricting cell proliferation potential were reestablished upon H1F0 re-expression. Moreover, deletion of CpG shore by genome editing resulted in a decrease in the H1F0 mRNA levels, this result indicates that H1F0 gene silencing in self-renewing tumor cells is, at least in part, due to the methylation of this enhancer region.

Some researches reported that H1F0 gene is a susceptibility gene associated with the taxol resistance (txr) phenotype. H1F0 binds to AR (androgen receptor) which is a transcription factor and uses AR as a major  enhancer of gene expression. As a prominent txr susceptibility gene candidate, the expression of H1F0 is down-regulated by silencing AR transcription factors. What’s more, there are some transcription factors involved in H1F0 expression activation and regulation. HBP1, a high-mobility group box transcription factor, interacted specifically with the H4-box in H1F0 promoter and involved in the activation of H1F0 gene expression, providing a link between the cell cycle control machinery and cell differentiation signals. The transcription factor NF-kappaB is actively involved in the regulation of H1F0 during differentiation.