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Nature. 2015 Feb 19;518(7539):344-9. doi: 10.1038/nature14233.

Transcription factor binding dynamics during human ES cell differentiation.

Author information

1
1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
2
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
3
1] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
4
1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Immunology, Weizmann Institute, Rehovot, 76100 Israel.

Abstract

Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome-wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage-specific behaviour of selected factors. In addition to the orchestrated remodelling of the chromatin landscape, we find that the binding of several transcription factors is strongly associated with specific loss of DNA methylation in one germ layer, and in many cases a reciprocal gain in the other layers. Taken together, our work shows context-dependent rewiring of transcription factor binding, downstream signalling effectors, and the epigenome during human embryonic stem cell differentiation.

PMID:
25693565
PMCID:
PMC4499331
DOI:
10.1038/nature14233
[Indexed for MEDLINE]
Free PMC Article
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