%0 Journal Article
%T Generation of bivalent chromatin domains during cell fate decisions
%A Marco De Gobbi
%A David Garrick
%A Magnus Lynch
%A Douglas Vernimmen
%A Jim R Hughes
%A Nicolas Goardon
%A Sidinh Luc
%A Karen M Lower
%A Jacqueline A Sloane-Stanley
%A Cristina Pina
%A Shamit Soneji
%A Raffaele Renella
%A Tariq Enver
%A Stephen Taylor
%A Sten Eirik W Jacobsen
%A Paresh Vyas
%A Richard J Gibbons
%A Douglas R Higgs
%J Epigenetics & Chromatin
%D 2011
%I BioMed Central
%R 10.1186/1756-8935-4-9
%X Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3.While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.In recent years it has been suggested that the epigenetic programme may play a key role in determining cell fate, including the decision to undergo self-renewal or commitment. Based on genome-wide chromatin immunoprecipitation (ChIP) studies combined with expression analysis, it has been suggested that the chromatin associated with many genes controlling lineage fate decisions is uniquely marked in stem cells. Their histone signature is referred to as bivalent as it includes modifications associated both with repression (H3K27me3) imposed by the polycomb group proteins (PcG), and activation (H3K4me3) encoded by the Set/MLL histone methyltransferase, the mammalian homologue of the trithorax group proteins (trxG) [1-6]. Despite having both 'active' and 'repressive' chromatin marks, such genes were thought not to be expressed. Taken together, these observations led to an attractive model suggesting that a preimposed epigenetic signature suppresses expression of lineage control genes in stem cells (maintaining
%U http://www.epigeneticsandchromatin.com/content/4/1/9