内蒙古大学李雪玲研究团队揭示了胎牛和成年牛中瘤胃组织特异性功能建立的表观遗传基础。这一研究成果于2024年11月5日在线发表在国际学术期刊《遗传学报》上。

研究人员对胎牛和成年牛组织以及多能干细胞的表观遗传和转录图谱进行了深入分析。在各个阶段和组织中广泛的甲基化差异中，研究人员鉴定出了特异性瘤胃差异甲基化区域（tsDMR），这些区域对调控上皮发育和能量代谢至关重要。这些tsDMR集中在超增强子区域，并与转录因子（TF）结合位点重叠。

回归模型表明，DNA甲基化以及H3K27me3和H3K27ac可以用于预测增强子活性。关键的上游转录因子，包括SOX2、FOSL1/2和SMAD2/3，主要通过双价修饰在胎儿发育过程中维持抑制状态。下游功能基因主要通过DNA甲基化维持稳定的抑制状态，直到分化完成。

该研究强调了tsDMR在调节瘤胃形态和功能的远端成分中的关键作用，为可能影响牛生产性状的表观遗传调控机制提供了重要见解。

据悉，反刍动物瘤胃是一种独特的器官，与模型物种中研究的其他组织相比，瘤胃的表观遗传调控在很大程度上仍未被探索。

附：英文原文

Title: Epigenetic basis for the establishment of ruminal tissue-specific functions in bovine fetuses and adults

Author: Xueling Li a

Issue&Volume: 2024/11/05

Abstract: Epigenetic regulation in the rumen, a unique ruminant organ, remains largely unexplored compared with other tissues studied in model species. In this study, we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells. Among the extensive methylation differences across various stages and tissues, we identify tissue-specific differentially methylated regions (tsDMRs) unique to the rumen, which are crucial for regulating epithelial development and energy metabolism. These tsDMRs cluster within super-enhancer regions that overlap with transcription factor (TF) binding sites. Regression models indicate that DNA methylation, along with H3K27me3 and H3K27ac, can be used to predict enhancer activity. Key upstream TFs, including SOX2, FOSL1/2, and SMAD2/3, primarily maintain an inhibitory state through bivalent modifications during fetal development. Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete. Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function, providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.

DOI: 10.1016/j.jgg.2024.10.008

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724002820