RT Journal Article
SR Electronic
T1 DNA methylation directs polycomb-dependent 3D genome re- organisation in naive pluripotency
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 527309
DO 10.1101/527309
A1 Katy A McLaughlin
A1 Ilya M Flyamer
A1 John P Thomson
A1 Heidi K Mjoseng
A1 Ruchi Shukla
A1 Iain Williamson
A1 Graeme R Grimes
A1 Robert S Illingworth
A1 Ian R Adams
A1 Sari Pennings
A1 Richard R Meehan
A1 Wendy A Bickmore
YR 2019
UL http://biorxiv.org/content/early/2019/01/22/527309.abstract
AB The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naive pluripotency by culturing in 2i conditions results in redistribution of polycomb (H3K27me3) away from its target loci. Here we demonstrate that 3D genome organisation is also altered in 2i. We found chromatin decompaction at polycomb target loci as well as loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground-state, we are able to restore the H3K27me3 distribution, and polycomb-mediated 3D genome organisation that is characteristic of primed ESCs grown in serum, to ESCs in 2i. However, these cells retain the functional characteristics of 2i ground state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organisation but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs.