Biological functions of DNA methyltransferase 1 require its methyltransferase activity
Biological functions of DNA methyltransferase 1 require its methyltransferase activity
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DOI：
10.1128/mcb.00036-07
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Bestor, Timothy H.
中科院分区：
文献类型：
--
作者：
Damelin, Marc;Bestor, Timothy H.
DNA甲基转移酶1（DNMT1）已被报道与多种因子相互作用，并含有内在的转录抑制活性。当在关键催化残基处引入保守点突变时，突变体DNMT 1不能拯救Dnmt 1缺失的胚胎干细胞（ES细胞）的任何表型，这表明DNMT 1的生物学功能是通过DNA甲基化来发挥的。表达突变蛋白的ES细胞不能在分化中存活。脑池内A颗粒家族反转录转座子不再甲基化，并在高水平转录。DNMT1的正确定位依赖于正常的基因组甲基化，我们讨论了这一发现对癌症表观遗传失调的影响。
DNA methyltransferase 1 (DNMT1) has been reported to interact with a wide variety of factors and to contain intrinsic transcriptional repressor activity. When a conservative point mutation was introduced at the key catalytic residue, mutant DNMT1 failed to rescue any of the phenotypes of Dnmt1-null embryonic stem (ES) cells, which indicated that the biological functions of DNMT1 are exerted through the methylation of DNA. ES cells that expressed the mutant protein did not survive differentiation. Intracisternal A-particle family retrotransposons were no longer methylated and were transcribed at high levels. The proper localization of DNMT1 depended on normal genomic methylation, and we discuss the implications of this finding for epigenetic dysregulation in cancer.