Transcription factor binding dynamics during human ES cell differentiation.

Nature
Authors
Keywords
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.

Year of Publication
2015
Journal
Nature
Volume
518
Issue
7539
Pages
344-9
Date Published
2015 Feb 19
ISSN
1476-4687
URL
DOI
10.1038/nature14233
PubMed ID
25693565
PubMed Central ID
PMC4499331
Links
Grant list
F32 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