Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis

Title: Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis
Authors: Rinaldi, LorenzoDatta, DebayanSerrat, JuditMatallanas, DavidKriegsheim, Alexander vonet al.
Permanent link: http://hdl.handle.net/10197/9819
Date: 6-Oct-2016
Online since: 2019-04-04T11:21:42Z
Abstract: The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both proteins prefer super-enhancers associated to genes that either define the ectodermal lineage or establish the stem cell and differentiated states. However, Dnmt3a and Dnmt3b differ in their mechanisms of enhancer regulation: Dnmt3a associates with p63 to maintain high levels of DNA hydroxymethylation at the center of enhancers in a Tet2-dependent manner, whereas Dnmt3b promotes DNA methylation along the body of the enhancer. Depletion of either protein inactivates their target enhancers and profoundly affects epidermal stem cell function. Altogether, we reveal novel functions for Dnmt3a and Dnmt3b at enhancers that could contribute to their roles in disease and tumorigenesis.
Funding Details: European Commission - Seventh Framework Programme (FP7)
European Research Council
Funding Details: Worldwide Cancer Research Foundation
Foundation La Marató de TV3
Spanish Ministry of Economy and Development
Foundation Vencer el Cancer (“Beat Cancer”)
Government of Cataluña
Foundation Fundación Botín
Institute for Research in Biomedicine (IRB-Barcelona)
AXA postdoctoral fellowship
Spanish Ministerio de Educación y Ciencia
Type of material: Journal Article
Publisher: Elsevier
Journal: Cell Stem Cell
Volume: 19
Issue: 4
Start page: 491
End page: 501
Copyright (published version): 2016 Elsevier
Keywords: Dnmt3aDnmt3bH3K36me3Tet2HydroxymethylationEpidermal Stem Cell homeostasis
DOI: 10.1016/j.stem.2016.06.020
Language: en
Status of Item: Peer reviewed
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:SBI Research Collection

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