Global Transcription in Pluripotent Embryonic Stem Cells

Sol Efroni, Radharani Duttagupta, Jill Cheng, Hesam Dehghani, Daniel J. Hoeppner, Chandravanu Dash, David P. Bazett-Jones, Stuart Le Grice, Ronald D.G. McKay, Kenneth H. Buetow, Thomas R. Gingeras, Tom Misteli, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

527 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)437-447
Number of pages11
JournalCell Stem Cell
Volume2
Issue number5
DOIs
StatePublished - 8 May 2008

Bibliographical note

Funding Information:
We thank Drs. Liran Carmel (NIH) and Robert Clifford (NIH) for help with statistical analysis, Dr. Mirek Dundr (Boston) for providing rDNA plasmids, and Dr. Bradley Bernstein for the ChIP-seq data shown in Figure S4 . This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; the Israel Science Foundation (215/07) (to E.M.); the European Union (IRG-206872) (to E.M.); Alon Fellowship (to E.M.); and an operating grant (to D.P.B.-J.) from the Canadian Institutes of Health Research. D.P.B.-J. holds a Canada Research Chair in Molecular and Cellular Imaging. Design and hybridization of all tiling arrays utilized in this study were supported by Affymetrix, Inc. R.D., J.C., and T.R.G. are employees of Affymetrix, Inc.

Keywords

  • STEMCELL

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