Postnatal DNA demethylation and its role in tissue maturation

Yitzhak Reizel, Ofra Sabag, Yael Skversky, Adam Spiro, Benjamin Steinberg, Diana Bernstein, Amber Wang, Julia Kieckhaefer, Catherine Li, Eli Pikarsky, Rena Levin-Klein, Alon Goren, Klaus Rajewsky, Klaus H. Kaestner, Howard Cedar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using. conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl-cytosine regulation as an epigenetic mechanism underlying cellular responses to. changing environment.

Original languageAmerican English
Article number2040
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

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