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Nature DOI:10.1038/nature14233

Transcription factor binding dynamics during human ES cell differentiation.

Publication TypeJournal Article
Year of Publication2015
AuthorsTsankov, AM, Gu, H, Akopian, V, Ziller, MJ, Donaghey, J, Amit, I, Gnirke, A, Meissner, A
Date Published2015 Feb 19
KeywordsCell Differentiation, Cell Lineage, Chromatin, Chromatin Assembly and Disassembly, DNA Methylation, Embryonic Stem Cells, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Genome, Human, Germ Layers, Histones, Humans, Protein Binding, Signal Transduction, Transcription Factors, Transcription, Genetic

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.


Alternate JournalNature
PubMed ID25693565
PubMed Central IDPMC4499331
Grant ListF32 DK095537 / DK / NIDDK NIH HHS / United States
5F32DK095537 / DK / NIDDK NIH HHS / United States
P01 GM099117 / GM / NIGMS NIH HHS / United States
U01ES017155 / ES / NIEHS NIH HHS / United States
P01GM099117 / GM / NIGMS NIH HHS / United States
P50HG006193 / HG / NHGRI NIH HHS / United States
U01 ES017155 / ES / NIEHS NIH HHS / United States