Genome-wide profiling of the epigenetic landscape of histone variant TH2B in murine oocytes and pre-implantation embryos.

Abstract

In brief: This study investigates the role of TH2B in pre-implantation embryos and found that TH2B deposition varies between gametes but rapidly redistributes in two-cell embryos after fertilization. Our ultra-low-input native chromatin immunoprecipitation and sequencing (ULI-NChIP-seq) revealed that TH2B is enriched in early chromatin but decreases after the two-cell stage, with strong correlations to key regulatory regions, histone modifications and transposable elements (TEs), indicating its critical role in zygotic genome activation and early developmental processes.

Abstract: The histone variant TH2B, enriched in oocytes, sperm and early embryos, decreases as embryos differentiate into pre-gastrula stages. Despite its presence, the role of TH2B in epigenetic reprogramming during early embryonic development remains largely under-researched. Our study employed ULI-NChIP-seq to analyze the genome-wide distribution of TH2B in metaphase II (MII) oocytes and early embryos. We found that TH2B is enriched in the chromatin of oocytes and two-cell stage embryos but becomes less prevalent after the two-cell stage. Correlation analysis revealed that the TH2B chromatin patterns in sperm and pre-implantation embryos are more similar to each other than to those in MII oocytes. Gene ontology (GO) analysis of TH2B-occupied loci linked them to various developmental processes including oogenesis, fertilization, chromatin modification and transcription regulation. The study also identified a strong association of TH2B with specific TEs, particularly long terminal repeats, which are known to regulate pre-implantation development. Additionally, early embryos showed H3K9me3 marks at TH2B-bound loci. TH2B exhibited strong correlations with H2A.Z and H3.3 in the two-cell and eight-cell stages, a positive association with H3K27Ac and H3K4me3 and a negative correlation with H3K27me3. Allelic reprogramming analysis of TH2B in embryos from C57BL/6J and DBA/2J crosses revealed differential dynamics between maternal and paternal alleles, with a notable paternal bias at the promoter in two-cell embryos. Thus, TH2B's enrichment in early embryonic stages and its association with key regulatory regions and histone modifications underscore its importance in zygotic genome activation and subsequent developmental processes.