|Title||Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1|
Lee, Ah Young
Szulwach, Keith E.
Lorincz, Matthew C.
|Affiliation||Univ Calif San Diego, Ludwig Inst Canc Res, Sch Med, La Jolla, CA 92093 USA.|
Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA.
Tsinghua Univ, Peking Univ, Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China.
Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
|Publisher||proceedings of the national academy of sciences of the united states of america|
|Citation||PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2014,111,(18),6690-6695.|
|Abstract||During mammalian development, DNA methylation patterns need to be reset in primordial germ cells (PGCs) and preimplantation embryos. However, many LTR retrotransposons and imprinted genes are impervious to such global epigenetic reprogramming via hitherto undefined mechanisms. Here, we report that a subset of such genomic regions are resistant to widespread erasure of DNA methylation in mouse embryonic stem cells (mESCs) lacking the de novo DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b. Intriguingly, these loci are enriched for H3K9me3 in mESCs, implicating this mark in DNA methylation homeostasis. Indeed, deletion of the H3K9 methyltransferase SET domain bifurcated 1 (Setdb1) results in reduced H3K9me3 and DNA methylation levels at specific loci, concomitant with increased 5-hydroxymethylation (5hmC) and ten-eleven translocation 1 binding. Taken together, these data reveal that Setdb1 promotes the persistence of DNA methylation in mESCs, likely reflecting one mechanism by which DNA methylation is maintained at LTR retrotransposons and imprinted genes during developmental stages when DNA methylation is reprogrammed.|
|Appears in Collections:||生命科学学院|