Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression.
AffiliationLymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom.
MetadataShow full item record
AbstractMany lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA Pol(II) is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
CitationEmbryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. 2011, 117 (1):83-7 Blood
- Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.
- Authors: Ko CI, Wang Q, Fan Y, Xia Y, Puga A
- Issue date: 2014 Jan
- Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.
- Authors: He J, Shen L, Wan M, Taranova O, Wu H, Zhang Y
- Issue date: 2013 Apr
- High histone acetylation and decreased polycomb repressive complex 2 member levels regulate gene specific transcriptional changes during early embryonic stem cell differentiation induced by retinoic acid.
- Authors: Lee ER, Murdoch FE, Fritsch MK
- Issue date: 2007 Sep
- Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.
- Authors: Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE
- Issue date: 2008 Oct
- The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation.
- Authors: Kalantry S, Mills KC, Yee D, Otte AP, Panning B, Magnuson T
- Issue date: 2006 Feb