Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. |
| |
Authors: | Gangning Liang Matilda F Chan Yoshitaka Tomigahara Yvonne C Tsai Felicidad A Gonzales En Li Peter W Laird Peter A Jones |
| |
Institution: | USC/Norris Comprehensive Cancer Center, Department of Urology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90089-9181, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
|
|