Generation of bivalent chromatin domains during cell fate decisions

Marco De Gobbi, David Garrick, Magnus Lynch, Douglas Vernimmen, Jim Hughes, Nicolas Goardon, Sidinh Luc, Karen Lower, Jackie Sloane-Stanley, Pina Cristina, Shamit Soneji, Raffaele Renella, Tariq Enver, Stephen Taylor, Sten Jacobsen, Paresh Vyas, Richard Gibbons, Doug Higgs

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)


    Background: In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined. Results: 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. Conclusions: 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.

    Original languageEnglish
    Article number9
    Number of pages12
    JournalEpigenetics and Chromatin
    Issue number9
    Publication statusPublished - 2011


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