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Macrohistone variants preserve cell identity by preventing the gain of H3K4me2 during reprogramming to pluripotency.

Abstract：

:Transcription-factor-induced reprogramming of somatic cells to pluripotency is a very inefficient process, probably due to the existence of important epigenetic barriers that are imposed during differentiation and that contribute to preserving cell identity. In an effort to decipher the molecular nature of these barriers, we followed a genome-wide approach, in which we identified macrohistone variants (macroH2A) as highly expressed in human somatic cells but downregulated after reprogramming to pluripotency, as well as strongly induced during differentiation. Knockdown of macrohistone variants in human keratinocytes increased the efficiency of reprogramming to pluripotency, whereas overexpression had opposite effects. Genome-wide occupancy profiles show that in human keratinocytes, macroH2A.1 preferentially occupies genes that are expressed at low levels and are marked with H3K27me3, including pluripotency-related genes and bivalent developmental regulators. The presence of macroH2A.1 at these genes prevents the regain of H3K4me2 during reprogramming, imposing an additional layer of repression that preserves cell identity.

journal_name

Cell Rep

journal_title

Cell reports

authors

Barrero MJ,Sese B,Kuebler B,Bilic J,Boue S,Martí M,Izpisua Belmonte JC

doi

10.1016/j.celrep.2013.02.029

subject

Has Abstract

pub_date

2013-04-25 00:00:00

pages

1005-11

issue

4

issn

2211-1247

pii

S2211-1247(13)00105-8

journal_volume

3

pub_type

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