Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
EMBO Rep. 2021 May 5;22(5):e51803. doi: 10.15252/embr.202051803. Epub 2021 Apr 12.
Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. These in vitro and in vivo discoveries are further supported by the finding that genes encoding DNA- and histone-modifying enzymes are often mutated in overlapping human diseases. Here, we summarize recent advances in understanding how DNA and histone methylation cooperate to maintain the cellular epigenomic landscape. We will also discuss the potential implication of these insights for understanding the etiology of, and developing biomarkers and therapies for, human congenital disorders and cancers that are driven by chromatin abnormalities.
胞嘧啶的 CpG 二核苷酸和组蛋白赖氨酸和精氨酸残基的甲基化是一种染色质修饰，对基因组完整性、复制和可及性的调控至关重要。DNA 和组蛋白甲基化的全基因组分布之间存在很强的相关性，这表明这些表观遗传标记之间存在密切关系。事实上，越来越多的文献揭示了 DNA 和组蛋白甲基化之间分子串扰的复杂机制。这些体外和体内的发现进一步得到了以下发现的支持，即编码 DNA 和组蛋白修饰酶的基因在重叠的人类疾病中经常发生突变。在这里，我们总结了最近在理解 DNA 和组蛋白甲基化如何合作以维持细胞表观基因组景观方面的进展。我们还将讨论这些见解对于理解由染色质异常驱动的人类先天性疾病和癌症的病因以及开发生物标志物和治疗方法的潜在意义。
