Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2013 Apr 25;3(4):1005-11. doi: 10.1016/j.celrep.2013.02.029. Epub 2013 Mar 28.

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

Author information

1
Center for Regenerative Medicine in Barcelona, Barcelona 08003, Spain.

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.

PMID:
23545500
DOI:
10.1016/j.celrep.2013.02.029
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center