" T; D* r$ V$ v. y（《细胞—干细胞》（Cell Stem Cell），Vol 2, 437-447, 08 May 2008，Sol Efroni, Eran Meshorer）3 _9 h4 X- O& o
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《细胞—干细胞》论文摘要# h% e, g$ g# D/ M- x+ N: X& L
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Cell Stem Cell, Vol 2, 437-447, 08 May 2008 9 G" y/ H2 D' h6 u; ~/ I2 y& V% G9 W4 X
ArticleGlobal Transcription in Pluripotent Embryonic Stem CellsSol Efroni,1,8 Radharani Duttagupta,2 Jill Cheng,2,10 Hesam Dehghani,3,11 Daniel J. Hoeppner,4 Chandravanu Dash,5 David P. Bazett-Jones,3 Stuart Le Grice,5 Ronald D.G. McKay,4 Kenneth H. Buetow,1 Thomas R. Gingeras,2 Tom Misteli,7,9, and Eran Meshorer6,8,9, % Y9 P g9 \: F" Z- V h: o
. B- O r( O) y4 ]$ h, d5 Q4 t+ Z( f1 National Cancer Institute Center for Bioinformatics, National Institutes of Health, Rockville, MD 20852, USA2 Affymetrix, Inc., 3380 Central Expressway, Santa Clara, CA 95051, USA3 The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada4 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20852, USA5 National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA6 Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel7 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA! [7 T4 J4 x& U) v- l2 f" T$ N. b
; f; q8 m! ?) \& G& _% h& ?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. $ v \- U0 x% r9 `( U P- j: |) {8 R; d9 p2 ~/ A# ]
Footnotes8 These authors contributed equally to this work. 9 O h+ m# Q- k/ c/ Y # z4 y! A% @: x p9 These authors contributed equally to this work as senior authors.) }1 A# s" ]! ^- H t
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10 Present address: Novartis Institutes for BioMedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.7 G/ X, o2 d: N
" Y6 n! F( M6 e# ]: a( v* H11 Present address: Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad 91775-1793, Iran. $ ]+ s; Y6 N: z9 ~' V. K( B. ~/ S9 p" D
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