DNA Hypomethylation Circuit of the Mouse Oocyte-Specific Histone H1foo Gene in Female Germ Cell Lineage1

Abstract

The oocyte-specific subtype of the linker histone H1 is H1FOO, which constitutes a major part of oocyte chromatin. H1foo is expressed in growing oocytes, through fertilization, up until the two-cell embryo stage, when it is subsequently replaced by somatic H1 subtypes. To elucidate whether an epigenetic mechanism is involved in the limited expression of H1foo, we analyzed the dynamics of the DNA methylation status of the H1foo locus in germ and somatic cells. We identified a tissue-dependent and differentially methylated region (T-DMR) upstream of the H1foo gene, which was hypermethylated in sperm, somatic cells, and stem cell lines. This region was specifically unmethylated in the ovulated oocyte, where H1foo is expressed. 5-Aza-2'-deoxycytidine treatments and luciferase assays provided in vitro evidence that DNA methylation plays a role in repressing H1foo in nonexpressing cells. DNA methylation analyses of fetal germ cells revealed the T-DMR to be hypomethylated in female and male germ cells at Embryonic Day 9.5 (E9.5), whereas it was highly methylated in somatic cells at this stage. Intriguingly, the unmethylated status was continuously observed throughout oogenesis at E9.5, E12.5, E15.5, E18.5, in mature oocytes, and after fertilization, in E3.5 blastocysts. In comparison, male germ cells acquired methylation beyond E18.5. These data demonstrate a continuously unmethylated circuit at the H1foo locus in the female germline.

Germline-specific H1 variants: the “sexy” linker histones

“…Additionally, DNA methylation also regulates H1oo transcription since the The similarity respect to mouse H1.2 is shown for each domain. The percentage of R residues respect to total basic residues (R+K) in the C-terminal tail is also shown H1oo gene contains a T-DMR region that is hypermethylated in somatic cells, sperm cells, and old embryos and, in contrast, is hypomethylated in oocytes and 1-2 cell embryos (Maeda et al 2008). …”

Oocyte maturation failure: a syndrome of bad eggs

“…For example, H1foo is an oocyte-specific subtype of the linker histone H1, which contributes to gene-specific regulation of transcription (34). Knockdown of H1foo resulted in oocyte arrest at metaphase I (35).…”

“…Knockdown of H1foo resulted in oocyte arrest at metaphase I (35). In vivo, H1foo function is mediated through methylation (34); therefore, it is possible that epigenetic modification of H1foo function may result in altered gene expression and oocyte maturation competence.…”

DNA methylation profile dynamics of tissue-dependent and differentially methylated regions during mouse brain development

“…T-DMRs have been found 3 ′ downstream of transcription start sites (TSSs) in addition to in 5 ′ -upstream promoter regions. A distinct combination of DNA methylation patterns at T-DMRs determines cellular identity during development [8-13], thus illustrating that DNA methylation profiles are unique to individual cells or tissue types [7,14,15]. …”