共 33 条
Macrohistone Variants Preserve Cell Identity by Preventing the Gain of H3K4me2 during Reprogramming to Pluripotency
被引:63
作者:

Barrero, Maria J.
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机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Sese, Borja
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h-index: 0
机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Kuebler, Bernd
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h-index: 0
机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Bilic, Josipa
论文数: 0 引用数: 0
h-index: 0
机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Boue, Stephanie
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h-index: 0
机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Marti, Merce
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机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain Ctr Regenerat Med Barcelona, Barcelona 08003, Spain

Izpisua Belmonte, Juan Carlos
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机构:
Ctr Regenerat Med Barcelona, Barcelona 08003, Spain
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA Ctr Regenerat Med Barcelona, Barcelona 08003, Spain
机构:
[1] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain
[2] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
来源:
关键词:
INACTIVE X-CHROMOSOME;
HISTONE MACROH2A1;
STEM-CELLS;
IDENTIFICATION;
GENERATION;
EFFICIENT;
CHROMATIN;
ISOFORMS;
BINDING;
DOMAIN;
D O I:
10.1016/j.celrep.2013.02.029
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
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.
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页码:1005 / 1011
页数:7
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