DNMT1,3A,3B:PRC2 methylates cytosine and histone H3

Stable Identifier
R-HSA-212269
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

DNA methyltransferases (DNMTs) associate with EZH2 of the Polycomb Repressive Complex 2 (PRC2) and methylate the 5 position of the cytosine ring in DNA (Vire et al. 2006). The histone methyltransferase activity of EZH2 also trimethylates lysine-27 of histone H3 (H3K27me3). The promoters of the MYT, WNT1, KCNA1, and CNR1 genes are methylated on cytosine by the DNMT:PRC2 complex however not all loci that have H3K27me3 by PRC2 also have cytosine methylation (Vire et al. 2006, Brinkman et al. 2012). DNA methylation and H3K27me3 appear to be mutually exclusive in CpG islands but are compatible throughout most of the rest of the genome (Brinkman et al. 2012). In mouse, DNA methylation and H3K27me3 appear to be antagonistic at most loci: loss of DNA methylation causes increased H3K27me3 while loss of PRC2 has little effect on DNA methylation (Hagarman et al. 2013). By competing with DNMT3a,b for association with PRC2, DNMT3L may antagonize DNA methylation at sites bound by PRC2 (Neri et al. 2013).

Literature References
PubMed ID Title Journal Year
22466170 Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk

Brinkman, AB, Gu, H, Bartels, SJ, Zhang, Y, Matarese, F, Simmer, F, Marks, H, Bock, C, Gnirke, A, Meissner, A, Stunnenberg, HG

Genome Res. 2012
16357870 The Polycomb group protein EZH2 directly controls DNA methylation

Viré, E, Brenner, C, Deplus, R, Blanchon, L, Fraga, M, Didelot, C, Morey, L, Van Eynde, A, Bernard, D, Vanderwinden, JM, Bollen, M, Esteller, M, Di Croce, L, de Launoit, Y, Fuks, F

Nature 2006
12435631 Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein

Kuzmichev, A, Nishioka, K, Erdjument-Bromage, H, Tempst, P, Reinberg, D

Genes Dev 2002
23326524 Coordinate regulation of DNA methylation and H3K27me3 in mouse embryonic stem cells

Hagarman, JA, Motley, MP, Kristjansdottir, K, Soloway, PD

PLoS ONE 2013
24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs

Neri, F, Krepelova, A, Incarnato, D, Maldotti, M, Parlato, C, Galvagni, F, Matarese, F, Stunnenberg, HG, Oliviero, S

Cell 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
DNA-methyltransferase activity of DNMT1,3A,3B:PRC2:Chromatin [nucleoplasm]
Physical Entity
Activity
Title
protein-lysine N-methyltransferase activity of DNMT1,3A,3B:PRC2:Chromatin [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created