Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes

Abstract

Heterochromatin protein (HP) 1γ, a component of heterochromatin in eukaryotes, is involved in H3K9 methylation. Although HP1γ is expressed strongly in neural tissues and neural stem cells, its functions are unclear. To elucidate the roles of HP1γ, we analyzed HP1γ ‐deficient (HP1γ KO) mouse embryonic neurospheres and determined that HP1γ KO neurospheres tended to differentiate after quaternary culture. Several genes normally expressed in neuronal cells were upregulated in HP1γ KO undifferentiated neurospheres, but not in the wild type (WT). Compared to that in the control neurospheres, the occupancy of H3K27me3 was lower around the transcription start sites (TSSs) of these genes in HP1γ KO neurospheres, while H3K9me2/3, H3K4me3, and H3K27ac amounts remained unchanged. Moreover, amounts of the H3K27me2/3 demethylases, UTX, and JMJD3, were increased around the TSSs of these genes. Treatment with GSK‐J4, an inhibitor of H3K27 demethylases, decreased the expression of genes upregulated in HP1γ KO neurospheres, along with an increase of H3K27me3 amounts. Therefore, in murine neurospheres, HP1γ protected the promoter sites of differentiated cell‐specific genes against H3K27 demethylases to repress the expression of these genes. A better understanding of central cellular processes such as histone methylation will help elucidate critical events such as cell‐specific gene expression, epigenetics, and differentiation.

Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging

“…Since heterochromatin that is characterized by H3K9me2 and binding of HP1γ is also associated with a histone de‐acetylation on H3K27 (Naruse et al, 2020; Wang et al, 2019), we sought to investigate whether inhibiting the de‐acetylation of histones in oocytes will cause a similar effect. Previous reports also showed that treatment with a histone deacetylase (HDAC) inhibitor affects oocyte maturation in vitro (Jin et al, 2014).…”

Loss of heterochromatin and retrotransposon silencing constitute an early phase in oocyte aging

“…5C, S9). Since heterochromatin that is characterized by H3K9me2 and binding of HP1γ is also associated with a histone de-acetylation on H3K27 (Naruse et al, 2020) (Wang et al, 2019), we sought to investigate whether inhibiting the deacetylation of histones in oocytes will cause a similar effect. Previous reports also showed that treatment with a histone deacetylase (HDAC) inhibitor affects oocyte maturation in-vitro (Jin et al, 2014).…”