title: Transcriptional and epigenetic dynamics during specification of human embryonic stem cells.
abstract: Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated hESCs. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Gifford
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ziller
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.forename: Cole
authors.initials: C
authors.lastname: Trapnell
authors.forename: Julie
authors.initials: J
authors.lastname: Donaghey
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsankov
authors.forename: Alex K
authors.initials: AK
authors.lastname: Shalek
authors.forename: David R
authors.initials: DR
authors.lastname: Kelley
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shishkin
authors.forename: Robbyn
authors.initials: R
authors.lastname: Issner
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Coyne
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fostel
authors.forename: Laurie
authors.initials: L
authors.lastname: Holmes
authors.forename: Jim
authors.initials: J
authors.lastname: Meldrim
authors.forename: Mitchell
authors.initials: M
authors.lastname: Guttman
authors.forename: Charles
authors.initials: C
authors.lastname: Epstein
authors.forename: Hongkun
authors.initials: H
authors.lastname: Park
authors.forename: Oliver
authors.initials: O
authors.lastname: Kohlbacher
authors.forename: John
authors.initials: J
authors.lastname: Rinn
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
mesh_terms: D000107:Acetylation; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones