The classic molecular model of cellular differentiation suggests that there is progressive closing of chromatin as cells transition from a progenitor state to a terminally differentiated state. In Science, Amit and colleagues develop a novel approach to chromatin immunoprecipitation (ChIP) called 'iChIP' that enables ChIP to be applied to only a few hundred cells. Notably, this level of sensitivity allows the examination of rare intermediate cell populations that are otherwise inaccessible to standard approaches. iChIP is used to examine the chromatin dynamics of enhancers and promoters in developing hematopoietic stem cells. A poised enhancer repertoire is established early in development and before the expression of transcriptional programs in differentiated cells. Collectively, the data present a modified picture of hematopoiesis, with enhancer potential peaking not at the stem cell stage but in the more oligoclonal progenitor cells.

Science (7 August 2014) 10.1126/science.1256271