Changes in the nuclear deposition of histone H2A variants during pre-implantation development in mice

Abstract

SUMMARYHistone H2A has several variants, and changes in chromatin composition associated with their replacement might involve chromatin structure remodeling. We examined the dynamics of the canonical histone H2A and its three variants, H2A.X, H2A.Z and macroH2A, in the mouse during oogenesis and pre-implantation development when genome remodeling occurs. Immunocytochemistry with specific antibodies revealed that, although H2A and all variants were deposited in the nuclei of fullgrown oocytes, only histone H2A.X was abundant in the pronuclei of one-cell embryos after fertilization, in contrast with the low abundance of histone H2A and the absence of H2A.Z. The decline in H2A and the depletion of H2A.Z and macroH2A after fertilization were confirmed using Flag epitope-tagged H2A, H2A.Z and macroH2A transgenic mouse lines. Microinjection experiments with mRNA encoding the Flag-tagged proteins revealed a similar pattern of nuclear incorporation of the H2A variants. Fusion protein experiments using H2A, H2A.Z and macroH2A fused with the C-terminal 23 amino acids of H2A.X showed that the C-terminal amino acids of H2A.X function specifically to target this variant histone into chromatin in embryos after fertilization and that the absence of H2A.Z and macroH2A from the chromatin is required for normal development. These results suggest that global changes in the composition of histone H2A variants in chromatin play a role in genome remodeling after fertilization.

Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation

“…In addition, asymmetric distribution of H3K36me3 and H3K79me2/3 are lost at the 1-cell stage, leading to global hypomethylation of these residues on both chromatins [39,40]. Furthermore, global replacement of histone variants, such as deposition of H3.3 to paternal chromatin as well as removal of H2A.Z and macroH2A from maternal chromatin [41,42], takes place soon after fertilization. These chromatin remodeling events might contribute to the derepression of TEs in zygotes.…”

Basic concepts of epigenetics

“…In contrast, core variant exchange with an H2A of greater stability is often associated with gene silencing, 106 such as in the case of H2ABbd or macroH2A-H2AB, which evoke inhibition of p300-dependent histone acetylation, attenuation of RNAP II and gene silencing. 107,108 Modifications to the H2B core are also involved in transcription control and include sumoylation, acetylation and ubiquitination.…”

Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality

“…Proteins which are present at levels not statistically different between groups A and B are indicated in light gray below the horizontal threshold line [49], as the most represented proteins in the secretome of the preimplantation human embryo able to predict positive pregnancy outcome [54]. Moreover, according to a recent observation describing the important role of histone H2A variants (H2A.X, H2A.Z and macroH2A) in genome remodeling after fertilization [55] and preimplantation embryo development [56], our study reveals that blastocoel fluid of aged woman undergoes a global change in histone composition, as it contains soluble histones (H2A.X, H2B and H4) that are completely absent in younger women.…”