State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestocks, Inner Mongolia University, Hohhot, Inner Mongolia 010070, China.
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestocks, Inner Mongolia University, Hohhot, Inner Mongolia 010070, China. E-mail:
Zool Res. 2024 Nov 18;45(6):1371-1384. doi: 10.24272/j.issn.2095-8137.2024.221.
DNA methylation at non-CG dinucleotides (mCH, H=A, C, T) widely occurs and plays an important role in specific cell types, including pluripotent, neural, and germ cells. However, the functions and regulatory mechanisms of mCH, particularly in species other than humans and mice, remain inadequately explored. In this study, we analyzed the distribution of mCH across different bovine tissues, identifying significantly elevated mCH levels in bovine embryonic stem cells (bESCs), as well as brain, spleen, and ileum tissues compared to other tissues. Marked differences in mCH patterns between somatic cells and bESCs were observed, reflecting distinct base preferences and the differential expression of DNA methyltransferases. We also identified exon methylation in both CG and non-CG contexts, resembling gene-associated methylation patterns observed in plants. To characterize tissue-specific variations in mCH, we developed a novel method for differential mCH analysis. Results indicated that mCH is not randomly distributed but tends to be enriched in tissue-specific functional regions. Furthermore, regression models demonstrated a positional correlation between CG methylation and mCH. This study enhances our understanding of mCH distribution and function in bovine somatic and stem cells, providing new insights into its potential roles across species and tissues. These findings advance knowledge of epigenetic mechanisms, shedding light on the potential involvement of mCH in development and disease processes.
非 CG 二核苷酸（mCH，H=A、C、T）的 DNA 甲基化广泛存在，并在特定细胞类型中发挥重要作用，包括多能性、神经和生殖细胞。然而，mCH 的功能和调控机制，特别是在人类和小鼠以外的物种中，仍未得到充分探索。在这项研究中，我们分析了 mCH 在不同牛组织中的分布，发现与其他组织相比，牛胚胎干细胞（bESC）以及脑、脾和回肠组织中的 mCH 水平显著升高。体细胞和 bESC 之间 mCH 模式存在明显差异，反映了不同的碱基偏好和 DNA 甲基转移酶的差异表达。我们还在 CG 和非 CG 背景下鉴定了外显子甲基化，类似于在植物中观察到的与基因相关的甲基化模式。为了描述 mCH 在组织特异性方面的变化，我们开发了一种用于差异 mCH 分析的新方法。结果表明，mCH 不是随机分布的，而是倾向于富集在组织特异性功能区域。此外，回归模型表明 CG 甲基化与 mCH 之间存在位置相关性。本研究增强了我们对牛体细胞和干细胞中 mCH 分布和功能的理解，为其在不同物种和组织中的潜在作用提供了新的见解。这些发现推进了对表观遗传机制的认识，揭示了 mCH 在发育和疾病过程中的潜在作用。
