TY - JOUR
T1 - XDnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs
AU - Neri, Francesco
AU - Krepelova, Anna
AU - Incarnato, Danny
AU - Maldotti, Mara
AU - Parlato, Caterina
AU - Galvagni, Federico
AU - Matarese, Filomena
AU - Stunnenberg, Hendrik G.
AU - Oliviero, Salvatore
N1 - Funding Information:
This work was supported by the Associazione Italiana Ricerca sul Cancro (AIRC) and Regione Toscana programma salute. We thank Dr. S. Yamanaka (Kyoto University, Japan) for providing the anti-Dnmt3L antibody, Dr. En Li (Novartis, China) for providing the Dnmt3a −/− Dnmt3b −/− ESCs and Dr. Dies Meijer for providing the Avi-tag plasmid and BirA ESCs.
PY - 2013/9/26
Y1 - 2013/9/26
N2 - Summary The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESCs), but its function in these cells is unknown. Through genome-wide analysis of Dnmt3L knockdown in ESCs, we found that Dnmt3L is a positive regulator of methylation at the gene bodies of housekeeping genes and, more surprisingly, is also a negative regulator of methylation at promoters of bivalent genes. Dnmt3L is required for the differentiation of ESCs into primordial germ cells (PGCs) through the activation of the homeotic gene Rhox5. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyltransferases Dnmt3a and Dnmt3b to maintain low methylation levels at the H3K27me3 regions. Thus, in ESCs, Dnmt3L counteracts the activity of de novo DNA methylases to maintain hypomethylation at promoters of bivalent developmental genes.
AB - Summary The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESCs), but its function in these cells is unknown. Through genome-wide analysis of Dnmt3L knockdown in ESCs, we found that Dnmt3L is a positive regulator of methylation at the gene bodies of housekeeping genes and, more surprisingly, is also a negative regulator of methylation at promoters of bivalent genes. Dnmt3L is required for the differentiation of ESCs into primordial germ cells (PGCs) through the activation of the homeotic gene Rhox5. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyltransferases Dnmt3a and Dnmt3b to maintain low methylation levels at the H3K27me3 regions. Thus, in ESCs, Dnmt3L counteracts the activity of de novo DNA methylases to maintain hypomethylation at promoters of bivalent developmental genes.
UR - http://www.scopus.com/inward/record.url?scp=84884827480&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2013.08.056
DO - 10.1016/j.cell.2013.08.056
M3 - Article
C2 - 24074865
AN - SCOPUS:84884827480
SN - 0092-8674
VL - 155
SP - 121
JO - Cell
JF - Cell
IS - 1
ER -