Global transcription in pluripotent embryonic stem cells.
The molecular mechanisms underlying pluripotency and lineage specification from embryonic stem cells (ESCs) are largely unclear. Differentiation pathways may be determined by the targeted activation of lineage-specific genes or by selective silencing of genome regions. Here we show that the ESC genome is transcriptionally globally hyperactive and undergoes large-scale silencing as cells differentiate. Normally silent repeat regions are active in ESCs, and tissue-specific genes are sporadically expressed at low levels. Whole-genome tiling arrays demonstrate widespread transcription in coding and noncoding regions in ESCs, whereas the transcriptional landscape becomes more discrete as differentiation proceeds. The transcriptional hyperactivity in ESCs is accompanied by disproportionate expression of chromatin-remodeling genes and the general transcription machinery. We propose that global transcription is a hallmark of pluripotent ESCs, contributing to their plasticity, and that lineage specification is driven by reduction of the transcribed portion of the genome.
Efroni
Sol
S
National Cancer Institute Center for Bioinformatics, National Institutes of Health, Rockville, MD 20852, USA.
Duttagupta
Radharani
R
Cheng
Jill
J
Dehghani
Hesam
H
Hoeppner
Daniel J
DJ
Dash
Chandravanu
C
Bazett-Jones
David P
DP
Le Grice
Stuart
S
McKay
Ronald D G
RD
Buetow
Kenneth H
KH
Gingeras
Thomas R
TR
Misteli
Tom
T
Meshorer
Eran
E
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D021901:DNA, Intergenic; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D021901:DNA, Intergenic