Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation

Abstract

Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factor bam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs. Furthermore, overexpression of mof reduces H1 association on chromatin. In contrast, the knocking down of mof significantly rescues the GSC loss phenotype. Taken together, these results suggest that H1 functions intrinsically to promote GSC self-renewal by antagonizing MOF function. Since H1 and H4K16 acetylation are highly conserved from fly to human, the findings from this study might be applicable to stem cells in other systems.

The replicative histone chaperone CAF1 is essential for the maintenance of identity and genome integrity in adult stem cells

“…The involvement of HP1a in this process corroborates recent findings in male GSCs, in which RNAi-mediated depletion of HP1 in germ cells leads to premature expression of bam in stem cells (Xing and Li, 2015). Interestingly, another epigenetic regulator, histone H1, was also recently shown to be required for the repression of bam transcription in female GSCs (Sun et al, 2015), highlighting the importance of the chromatin environment to regulate cell fate in GSCs.…”

Emerging roles of linker histones in regulating chromatin structure and function

“…In this case, H1 regulates H4K16ac by antagonizing the H3K16-specific HAT MOF (FIG. 4a), depletion of which rescued H1-knockdown phenotypes 81 . In addition, the interaction between H1 and histone deacetylases (HDACs) may contribute to the negative correlation between H1 and core histone acetylation.…”

“…4a). Furthermore, H1 is required for the maintenance of female germline stem cells in D. melanogaster , where its depletion selectively augments H4K16 acetylation (H4K16ac), causing premature differentiation 81 . In this case, H1 regulates H4K16ac by antagonizing the H3K16-specific HAT MOF (FIG.…”

Compensatory replacement of the BigH1 variant histone by canonical H1 supports normal embryonic development in Drosophila

“…Instead, prior functional studies of H1 relies on RNAi knock-down or overexpression approaches. It has been shown that H1 is important for the maintenance of heterochromatin stability and gene expression (Ni et al 2006;Lu et al 2009Lu et al , 2013Vujatovic et al 2012), the S e p t e m b e r 4 , 2 0 1 9 5 regulation of DNA replication in polyploid cells (Andreyeva et al 2017), the compaction of chromatin in endo-replicating cells (Corona et al 2007;Lu et al 2009;Siriaco et al 2015), and stem cell maintenance in testis (Sun et al 2015).…”