Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming

作者：West Jason A; Cook April; Alver Burak H; Stadtfeld Matthias; Deaton Aimee M; Hochedlinger Konrad; Park Peter J^*; Tolstorukov Michael Y; Kingston Robert E

来源：Nature Communications, 2014, 5(1): 4719.

DOI：10.1038/ncomms5719

Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes.

• 出版日期2014-8