Genomic architecture of histone 3 lysine 27 trimethylation during late ovine skeletal muscle development

Abstract

SummaryThe ruminant developmental transition from late foetus to lamb is associated with marked changes in skeletal muscle structure and function that reflect programming for new physiological demands following birth. To determine whether epigenetic changes are involved in this transition, we investigated the genomic architecture of the chromatin modification, histone 3 lysine 27 trimethylation (H3K27me3), which typically regulates early life developmental processes; however, its role in later life processes is unclear. Chromatin immunoprecipitation coupled with next‐generation sequencing was used to map H3K27me3 nucleosomes in ovine longissimus lumborum skeletal muscle at 100 days of gestation and 12 weeks post‐partum. In both states, H3K27me3 modification was associated with genes, transcription start sites and CpG islands and with transcriptional silencing. The H3K27me3 peaks consisted of two major categories, promoter specific and regional, with the latter the dominant feature. Genes encoding homeobox transcription factors regulating early life development and genes involved in neural functions, particularly gated ion channels, were strongly modified by H3K27me3. Gene promoters differentially modified by H3K27me3 in the foetus and lamb were enriched for gated ion channels, which may reflect changes in neuromuscular function. However, most modified genes showed no changes, indicating that H3K27me3 does not have a large role in late muscle maturation. Notably, promyogenic transcription factors were strongly modified with H3K27me3 but showed no differences between the late gestation foetus and lamb, likely reflecting their lack of involvement in the myofibre fusion process occurring in this transition. H3K27me3 is a major architectural feature of the epigenetic landscape of ruminant skeletal muscle, and it comments on gene transcription and gene function in the context of late skeletal muscle development.

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“…The recent Functional Annotation of Animal Genomes (FAANG) initiative has begun to generate high-resolution epigenetic maps for a number of mammalian production species and tissues, especially sheep and cattle (13), and will provide additional detailed species-specific information. Genome-wide mapping of specific chromatin modifications and DNA methylation in a limited tissue range from sheep and cattle has also been undertaken (59,441,444).…”

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“…The H3 histone tail of amino acids mostly comprise of lysine and arginine [14]. Trimethylation of histone H3 at lysine 27 (H3K27me3) is an epigenetic mark associated with gene silencing, and often found in the promoter of developmental genes [15]. Enhancer of zeste homolog 2 (EZH2) histone methyltransferase, a catalytic subunit of Polycomb repressive complex 2 (PRC2), is responsible for catalyzing the methylation of H3K27, thereby resulting in gene silencing [16].…”

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“…ChIP-chip experiments form developmental transition from late fetus to lamb during late ovine skeletal muscle development reveal that H3K27me 3 modification is associated with genes, transcription start sites (TSS) and CpG islands and with transcriptional silencing. Most modified genes have no changes during the muscle transition, indicating that H3K27me 3 does not have a large role in late muscle maturation [77] . These findings suggest that H3K27me 3 represses developmental genes at initial embryonic stages.…”