Open AccessCooperativity between DNA Methyltransferases in the Maintenance Methylation of Repetitive Elements
Author(s) -
Gangning Liang,
Matilda F. Chan,
Yoshitaka Tomigahara,
Yvonne Tsai,
Felicidad A. Gonzales,
En Li,
Peter W. Laird,
Peter A. Jones
Publication year - 2002
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.22.2.480-491.2002
Subject(s) - biology , dna methylation , methyltransferase , methylation , rna directed dna methylation , cpg site , dnmt1 , epigenomics , dna methyltransferase , dnmt3b , microbiology and biotechnology , epigenetics of physical exercise , genetics , dna , gene , gene expression
We used mouse embryonic stem (ES) cells with systematic gene knockouts for DNA methyltransferases to delineate the roles of DNA methyltransferase 1 (Dnmt1) and Dnmt3a and -3b in maintaining methylation patterns in the mouse genome. Dnmt1 alone was able to maintain methylation of most CpG-poor regions analyzed. In contrast, both Dnmt1 and Dnmt3a and/or Dnmt3b were required for methylation of a select class of sequences which included abundant murine LINE-1 promoters. We used a novel hemimethylation assay to show that even in wild-type cells these sequences contain high levels of hemimethylated DNA, suggestive of poor maintenance methylation. We showed that Dnmt3a and/or -3b could restore methylation of these sequences to pretreatment levels following transient exposure of cells to 5-aza-CdR, whereas Dnmt1 by itself could not. We conclude that ongoing de novo methylation by Dnmt3a and/or Dnmt3b compensates for inefficient maintenance methylation by Dnmt1 of these endogenous repetitive sequences. Our results reveal a previously unrecognized degree of cooperativity among mammalian DNA methyltransferases in ES cells.