Chromatin Accessibility Dynamics During Reprogramming
37 Pages Posted: 4 Apr 2018 Sneak Peek Status: PublishedMore...
Cell fate decisions remain poorly understood at the chromatin level. Here we report a dynamic logic for chromatin remodeling during reprogramming. Global mapping of accessible chromatin loci in MEFs expressing Oct4-Sox2-Klf4 by ATAC-seq reveals dynamic changes from open to closed (OC) and closed to open (CO), with a burst of OC in the beginning and a climax CO at the end. We then show that factors/conditions known to impede reprogramming prevent OSK-driven OC and skew the overall OC-CO dynamics. Mechanistically, while the CO loci are enriched with and opened by Oct4-Sox2-Klf4 directly, the OC loci are devoid of them suggesting an indirect OC process. Indeed, we show that Sap30 is activated early and plays a key role in the OC process. These results reveal a chromatin accessibility logic during reprogramming and identify Sap30 as one of the first responders critical for the prerequisite silencing of somatic genes.
Suggested Citation: Suggested Citation