DNA methylation is an important covalent modification of mammalian genomic DNA that represses transcription. Genomic DNA is mostly maintained with high amounts of methylation, but some regions such as CpG islands are nearly perpetually unmethylated. Recently, large valleys or canyons of unmethylated DNA were discovered throughout the mammalian genome (1, 2). Most are associated with conserved developmental regulators, such as homeobox genes, and are thought to be actively regulated. The size of these canyons is maintained by a push and pull interplay between DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) dioxygenases that oxidize 5-methylcytosine, which leads to demethylation (2). On page 146 of this issue, Dixon et al. (3) identify QSER1 (glutamine and serine–rich protein 1) as part of the “push” protection mechanism that restricts DNA methylation. They show that QSER1 cooperates with TET1 by antagonizing chromatin binding of DNMT3A and DNMT3B, thus helping to retain the developmental potential of stem cells.

DNA甲基化是抑制转录的哺乳动物基因组DNA的重要共价修饰。基因组 DNA 大多保持大量甲基化，但某些区域（如 CpG 岛）几乎永远未甲基化。最近，在整个哺乳动物基因组中发现了未甲基化 DNA 的大山谷或峡谷 ( 1 , 2 )。大多数与保守的发育调节因子有关，例如同源盒基因，并被认为受到积极调节。这些峡谷的大小是通过 DNA 甲基转移酶 (DNMT) 和 10-11 易位 (TET) 双加氧酶之间的推拉相互作用来维持的，后者可氧化 5-甲基胞嘧啶，从而导致去甲基化 ( 2 )。在本期第 146 页，Dixon等人。( 3 ) 将 QSER1（富含谷氨酰胺和丝氨酸的蛋白质 1）鉴定为限制 DNA 甲基化的“推动”保护机制的一部分。他们表明，QSER1 通过拮抗 DNMT3A 和 DNMT3B 的染色质结合来与 TET1 合作，从而有助于保持干细胞的发育潜力。