Revisiting Heterochromatin in Embryonic Stem Cells 英文参考文献.docVIP

Perspective RevisitingHeterochromatininEmbryonicStemCells IrinaStancheva* Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom It is widely believed that chromatin in embryonic stem (ES) cells exists in a unique ‘‘open’’ conformation, character- ized by sparse, disorganized heterochro- matin and prevalent global transcription. Upon differentiation, this ‘‘blueprint’’ of pluripotent state is thought to undergo dramaticremodelling.InthisissueofPLoS Genetics, Lienert and colleagues [1] revisit heterochromatinandtranscriptioninplu- ripotentandterminallydifferentiatedcells todemonstratethatneithertheabundance ofrepressivehistoneH3lysine9dimethy- lation (H3K9me2) nor the net transcrip- tional output of the genome discriminate thesetwoverydifferentcellstates. Pluripotent ES cells, derived from the innercellmassofdevelopingmammalian blastocyst, have the distinctive ability to self-renewincultureanddifferentiateinto multiplelineageswhenexposedtoappro- priate signals. The self-organizing regula- tory network of transcription factors and the epigenetic mechanisms that are in- volvedinmaintenanceofpluripotentstate and self-renewal are actively debated and intensively studied by many laboratories [2,3]. When induced to differentiate, ES cells respond by changes in gene expres- sion, cell morphology, and chromatin structure, which may collectively contrib- ute to a reduction in developmental plasticity[4,5]. Severallinesofevidencehavesuggested thatDNAinstemcellsispackagedintoan unusuallydynamicformofchromatinthat carriesEScell–specificpatternsofhistone modifications. Thus, in ES cells, histone H3 and H4 tend to be hyperacetylated; constitutiveheterochromatinfoci,marked by histone H3 lysine 9 trimethylation (H3K9me3), are fewer and less well organized; and histone and non-histone chromatin-boundproteins,suchashetero- chromatin protein 1 (HP1), are more mobile [4,6,7]. In addition, a substantial number of gene promoters in ES c