Transcription factor binding dynamics during human ESC differentiation

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.

[1]  Charles Elkan,et al.  Fitting a Mixture Model By Expectation Maximization To Discover Motifs In Biopolymer , 1994, ISMB.

[2]  J. Massagué,et al.  Physical and Functional Interaction of SMADs and p300/CBP* , 1998, The Journal of Biological Chemistry.

[3]  A. Simeone,et al.  Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. , 1999, Development.

[4]  A. Órfão,et al.  Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway. , 2002, Blood.

[5]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[6]  S. Pikkarainen,et al.  GATA transcription factors in the developing and adult heart. , 2004, Cardiovascular research.

[7]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[8]  M. Koch,et al.  Otx2 Regulates Subtype Specification and Neurogenesis in the Midbrain , 2005, The Journal of Neuroscience.

[9]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[10]  T. Mikkelsen,et al.  Genome-scale DNA methylation maps of pluripotent and differentiated cells , 2008, Nature.

[11]  K. Zaret.  Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation , 2008, Nature Reviews Genetics.

[12]  Catherine Payne,et al.  Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling , 2008, Proceedings of the National Academy of Sciences.

[13]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[14]  M. Tomishima,et al.  Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling , 2009, Nature Biotechnology.

[15]  M. Tomishima,et al.  Derivation of neural crest cells from human pluripotent stem cells , 2010, Nature Protocols.

[16]  C. Glass,et al.  Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. , 2010, Molecular cell.

[17]  G. Bourque,et al.  Transposable elements have rewired the core regulatory network of human embryonic stem cells , 2010, Nature Genetics.

[18]  K. Schenke-Layland,et al.  Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells , 2010, Proceedings of the National Academy of Sciences.

[19]  Eric S. Lander,et al.  Comparative Epigenomic Analysis of Murine and Human Adipogenesis , 2010, Cell.

[20]  M. Araúzo-Bravo,et al.  FGF signalling inhibits neural induction in human embryonic stem cells , 2011, The EMBO journal.

[21]  Vijay K. Tiwari,et al.  DNA-binding factors shape the mouse methylome at distal regulatory regions , 2011, Nature.

[22]  M. Trotter,et al.  Pluripotency factors regulate definitive endoderm specification through eomesodermin. , 2011, Genes & development.

[23]  S. Henikoff,et al.  Epigenome characterization at single base-pair resolution , 2011, Proceedings of the National Academy of Sciences.

[24]  Richard A Young,et al.  Control of the Embryonic Stem Cell State , 2011, Cell.

[25]  Ryan A. Flynn,et al.  A unique chromatin signature uncovers early developmental enhancers in humans , 2011, Nature.

[26]  Matt Thomson,et al.  Pluripotency Factors in Embryonic Stem Cells Regulate Differentiation into Germ Layers , 2011, Cell.

[27]  David A. Orlando,et al.  Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling , 2011, Cell.

[28]  Joseph K. Pickrell,et al.  False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions , 2011, Bioinform..

[29]  N. Friedman,et al.  Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis , 2011, Cell.

[30]  Peter A. Jones,et al.  OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes , 2011, Proceedings of the National Academy of Sciences.

[31]  J. Carroll,et al.  Pioneer transcription factors: establishing competence for gene expression. , 2011, Genes & development.

[32]  David Z. Chen,et al.  Architecture of the human regulatory network derived from ENCODE data , 2012, Nature.

[33]  Shane J. Neph,et al.  An expansive human regulatory lexicon encoded in transcription factor footprints , 2012, Nature.

[34]  Peter A. C. 't Hoen,et al.  Accounting for immunoprecipitation efficiencies in the statistical analysis of ChIP-seq data , 2013, BMC Bioinformatics.

[35]  Matthew T. Maurano,et al.  Widespread plasticity in CTCF occupancy linked to DNA methylation , 2012, Genome research.

[36]  T. Bailey,et al.  Inferring direct DNA binding from ChIP-seq , 2012, Nucleic acids research.

[37]  A. Gnirke,et al.  Charting a dynamic DNA methylation landscape of the human genome , 2013, Nature.

[38]  Irene Cantone,et al.  Epigenetic programming and reprogramming during development , 2013, Nature Structural &Molecular Biology.

[39]  R. Young,et al.  Super-Enhancers in the Control of Cell Identity and Disease , 2013, Cell.

[40]  David A. Orlando,et al.  Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes , 2013, Cell.

[41]  Juan M. Vaquerizas,et al.  DNA-Binding Specificities of Human Transcription Factors , 2013, Cell.

[42]  Michael J. Ziller,et al.  Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells , 2013, Cell.

[43]  The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity , 2013, Cell.

[44]  Zachary D. Smith,et al.  DNA methylation: roles in mammalian development , 2013, Nature Reviews Genetics.

[45]  Michael Q. Zhang,et al.  Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells , 2013, Cell.

[46]  Ludovic Vallier,et al.  The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity , 2014, Cell.

[47]  A. Simeone,et al.  Reorganization of enhancer patterns in transition from naive to primed pluripotency. , 2014, Cell stem cell.

[48]  D. Odom,et al.  Evolution of transcription factor binding in metazoans — mechanisms and functional implications , 2014, Nature Reviews Genetics.

[49]  N. Friedman,et al.  Chromatin state dynamics during blood formation , 2014, Science.

[50]  Michael Q. Zhang,et al.  Integrative analysis of 111 reference human epigenomes , 2015, Nature.