Journal article
Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment
Melanie A Eckersley-Maslin, Aled Parry, Marloes Blotenburg, Christel Krueger, Yoko Ito, Valar Nila Roamio Franklin, Masashi Narita, Clive S D'Santos, Wolf Reik
NATURE STRUCTURAL & MOLECULAR BIOLOGY | NATURE RESEARCH | Published : 2020
Abstract
How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion ..
View full abstractGrants
Awarded by BBSRC Discovery Fellowship
Awarded by EMBO Fellowship
Awarded by Sir Henry Wellcome Fellowship
Awarded by Cancer Research UK Cambridge Institute Core grant
Awarded by Biotechnology and Biological Sciences Research Council
Awarded by Wellcome Trust
Funding Acknowledgements
We thank all members of the Reik laboratory for helpful discussions. We also thank F. di Tullio for help generating overexpression cell lines, F. Krueger for processing sequencing data and for general bioformatics support, S. Wingett for bioinformatic assistance and S. Andrews for bioinformatic advice. We thank B. Hussey and E. Easthope at Sanger Institute and K. Tabbada at Babraham Institute for assistance with high-throughput sequencing, R. Walker for assistance with flow cytometry, and J. Webster and D. Oxley for mass spectrometry. Dnmt TKO cells were a kind gift from D. Schubeler (FMI). M.A.E.-M. is supported by a BBSRC Discovery Fellowship (BB/T009713/1) and was supported by an EMBO Fellowship (ALTF938-2014) and a Marie Sklodowska-Curie Individual Fellowship. A.P. is supported by a Sir Henry Wellcome Fellowship (215912/Z/19/Z). M.B. was supported by an Erasmus Grant. M.N. and Y.I. were supported by a Cancer Research UK Cambridge Institute Core grant (no. C9545/A29580). Research in the Reik laboratory is supported by the Biotechnology and Biological Sciences Research Council (BB/K010867/1) and the Wellcome Trust (095645/Z/11/Z).