Transcription factor binding dynamics during human ES cell differentiation

Alexander M. Tsankov, Hongcang Gu, Veronika Akopian, Michael J. Ziller, Julie Donaghey, Ido Amit, Andreas Gnirke and Alexander Meissner ()
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Alexander M. Tsankov: Broad Institute of MIT and Harvard
Hongcang Gu: Broad Institute of MIT and Harvard
Veronika Akopian: Harvard Stem Cell Institute
Michael J. Ziller: Broad Institute of MIT and Harvard
Julie Donaghey: Broad Institute of MIT and Harvard
Ido Amit: Broad Institute of MIT and Harvard
Andreas Gnirke: Broad Institute of MIT and Harvard
Alexander Meissner: Broad Institute of MIT and Harvard

Nature, 2015, vol. 518, issue 7539, 344-349

Abstract: 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.

Date: 2015
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DOI: 10.1038/nature14233

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