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

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

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

2014
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Overview
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. Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al . explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.