title: Control of developmental regulators by Polycomb in human embryonic stem cells.
abstract: Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. These genes are occupied by nucleosomes trimethylated at histone H3K27, are transcriptionally repressed, and contain some of the most highly conserved noncoding elements in the genome. We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes. These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jenner
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Boyer
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Guenther
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Levine
authors.forename: Roshan M
authors.initials: RM
authors.lastname: Kumar
authors.forename: Brett
authors.initials: B
authors.lastname: Chevalier
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Johnstone
authors.forename: Megan F
authors.initials: MF
authors.lastname: Cole
authors.forename: Kyo-ichi
authors.initials: K
authors.lastname: Isono
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Takuya
authors.initials: T
authors.lastname: Fuchikami
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.forename: Heather L
authors.initials: HL
authors.lastname: Murray
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Zucker
authors.forename: Bingbing
authors.initials: B
authors.lastname: Yuan
authors.forename: George W
authors.initials: GW
authors.lastname: Bell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Herbolsheimer
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hannett
authors.forename: Kaiming
authors.initials: K
authors.lastname: Sun
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Volkert
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
authors.forename: David K
authors.initials: DK
authors.lastname: Gifford
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; C430461:SUZ12 protein, human; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2; D012319:RNA Polymerase II