Control of developmental regulators by Polycomb in human embryonic stem cells.
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.
Lee
Tong Ihn
TI
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Jenner
Richard G
RG
Boyer
Laurie A
LA
Guenther
Matthew G
MG
Levine
Stuart S
SS
Kumar
Roshan M
RM
Chevalier
Brett
B
Johnstone
Sarah E
SE
Cole
Megan F
MF
Isono
Kyo-ichi
K
Koseki
Haruhiko
H
Fuchikami
Takuya
T
Abe
Kuniya
K
Murray
Heather L
HL
Zucker
Jacob P
JP
Yuan
Bingbing
B
Bell
George W
GW
Herbolsheimer
Elizabeth
E
Hannett
Nancy M
NM
Sun
Kaiming
K
Odom
Duncan T
DT
Otte
Arie P
AP
Volkert
Thomas L
TL
Bartel
David P
DP
Melton
Douglas A
DA
Gifford
David K
DK
Jaenisch
Rudolf
R
Young
Richard A
RA
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
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