Byrne K, McWilliam S, Vuocolo T, Gondro C, Cockett N E, Tellam R L
CSIRO Animal, Food and Health Sciences, Queensland Bioscience Precinct, 306 Carmody Rd, St Lucia, QLD, 4067, Australia.
Anim Genet. 2014 Jun;45(3):427-38. doi: 10.1111/age.12145. Epub 2014 Mar 27.
The 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.
反刍动物从晚期胎儿到羔羊的发育转变与骨骼肌结构和功能的显著变化相关，这些变化反映了出生后对新生理需求的编程。为了确定表观遗传变化是否参与了这一转变，我们研究了染色质修饰组蛋白3赖氨酸27三甲基化（H3K27me3）的基因组结构，它通常调节生命早期的发育过程；然而，其在生命后期过程中的作用尚不清楚。采用染色质免疫沉淀结合下一代测序技术，绘制妊娠100天和产后12周绵羊腰最长肌骨骼肌中H3K27me3核小体图谱。在这两种状态下，H3K27me3修饰均与基因、转录起始位点和CpG岛以及转录沉默相关。H3K27me3峰主要分为两类，即启动子特异性峰和区域峰，后者是主要特征。编码调节生命早期发育的同源框转录因子的基因以及参与神经功能（特别是门控离子通道）的基因被H3K27me3强烈修饰。在胎儿和羔羊中被H3K27me3差异修饰的基因启动子富含门控离子通道，这可能反映了神经肌肉功能的变化。然而，大多数修饰基因没有变化，表明H3K27me3在肌肉后期成熟中作用不大。值得注意的是，促肌生成转录因子被H3K27me3强烈修饰，但在妊娠晚期胎儿和羔羊之间没有差异，这可能反映了它们在这一转变过程中不参与肌纤维融合过程。H3K27me3是反刍动物骨骼肌表观遗传景观的一个主要结构特征，它在骨骼肌后期发育的背景下对基因转录和基因功能进行了注释。
