title: Transcription factor binding dynamics during human ES cell differentiation.
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.
authors.affiliation: 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.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tsankov
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.affiliation: 1] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Akopian
authors.affiliation: 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.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ziller
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: Donaghey
authors.affiliation: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Immunology, Weizmann Institute, Rehovot, 76100 Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.affiliation: 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.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D057890:Epigenomics; D015894:Genome, Human / Q000235:genetics; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors