Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin-SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs.

Original publication

DOI

10.1101/gad.255984.114

Type

Journal article

Journal

Genes dev

Publication Date

01/04/2015

Volume

29

Pages

702 - 717

Keywords

Activin/Nodal, DPY30, H3K4me3, NANOG, SMAD2/3, hESCs, Activins, Animals, Cell Differentiation, Cells, Cultured, Chromatin, Embryo, Mammalian, Embryonic Stem Cells, Epigenesis, Genetic, Histone Methyltransferases, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Mice, Nanog Homeobox Protein, Nodal Protein, Signal Transduction, Smad2 Protein, Smad3 Protein