Mouse Oocytes and Early Embryos Express Multiple Histone H1 Subtypes1

Abstract

Oocytes and embryos of many species, including mammals, contain a unique linker (H1) histone, termed H1oo in mammals. It is uncertain, however, whether other H1 histones also contribute to the linker histone complement of these cells. Using immunofluorescence and radiolabeling, we have examined whether histone H10, which frequently accumulates in the chromatin of nondividing cells, and the somatic subtypes of H1 are present in mouse oocytes and early embryos. We report that oocytes and embryos contain mRNA encoding H10. A polymerase chain reaction-based test indicated that the poly(A) tail did not lengthen during meiotic maturation, although it did so beginning at the four-cell stage. Antibodies raised against histone H10 stained the nucleus of wild-type prophase-arrested oocytes but not of mice lacking the H10 gene. Following fertilization, H10 was detected in the nuclei of two-cell embryos and less strongly at the four-cell stage. No signal was detected in H10 -/- embryos. Radiolabeling revealed that species comigrating with the somatic H1 subtypes H1a and H1c were synthesized in maturing oocytes and in one- and two-cell embryos. Beginning at the four-cell stage in both wild-type and H10 -/- embryos, species comigrating with subtypes H1b, H1d, and H1e were additionally synthesized. These results establish that histone H10 constitutes a portion of the linker histone complement in oocytes and early embryos and that changes in the pattern of somatic H1 synthesis occur during early embryonic development. Taken together with previous results, these findings suggest that multiple H1 subtypes are present on oocyte chromatin and that following fertilization changes in the histone H1 complement accompany the establishment of regulated embryonic gene expression.

Histone H1 Variants Are Differentially Expressed and Incorporated into Chromatin during Differentiation and Reprogramming to Pluripotency

“…Therefore, in humans this variant appears to be specific to pluripotent cells, although it represents a small percentage of the total H1 content in these cells. Indeed the H1.1 expression is restricted to a few tissues in the adult mouse but has also been detected in mouse oocytes and early embryos, in male germ cells during early stages of spermatogenesis, and in several tissues shortly after birth (36,37). Despite the fact that the occupancy of the H1.1 promoter by pluripotency factors has been described in genome wide approaches (19), we did not detect their presence at the reported site.…”

The Pronuclei - 20 Years Later

“…As far as both pronuclei are concerned, a particular localisation of selected acetylated forms of histones h3 and h2A was detected at the nuclear periphery of one and two-cell stage embryos (39). establishment of regulated gene expression in both pronuclei and blastomeres is also associated to the presence of a particular complement of histone h1 subtypes (15). The dynamics of histone modifications is likely to be controlled at the mRnA processing level as a special category of stem-loop binding proteins (SlBP) protecting transcripts from degradation display abundant accumulation in pronuclei and cytoplasm during the first cell cycle (3).…”

Dynamic alterations of linker histone variants during development

“…We have described the gradual disappearance of somatic H1 following the mitotic stage of oogenesis, and the available evidence supports its nearly complete absence from the oocyte by the time of meiosis arrest. While mRNA encoding for all six of the somatic subtypes of H1 could be detected in GV-stage oocytes of Xenopus, none of their corresponding proteins were found to be present using immunological techniques, with the exception of histone H1 o (Hock et al, 1993;Clarke et al, 1997;Clarke et al, 1998;Fu et al, 2003). It was later shown that injected somatic H1 was not able to localize properly in mouse oocyte chromatin, compared to H1oo .…”

“…Following this point, the model systems we have been using to describe oogenesis differ widely from each other. In mouse, and presumably humans, most of the somatic histones make their reappearance following the next mitotic division, during the four-cell stage of embryogenesis (Fu et al, 2003). In Xenopus, however, oocyte-specific histone will remain the predominant linker histone until much later in development, at the mid-blastula transition, or MBT (Dimitrov et al, 1993;Fig.…”