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Publication : Chromatin Accessibility Dynamics during iPSC Reprogramming.

First Author  Li D Year  2017
Journal  Cell Stem Cell Volume  21
Issue  6 Pages  819-833.e6
PubMed ID  29220666 Mgi Jnum  J:253974
Mgi Id  MGI:6101310 Doi  10.1016/j.stem.2017.10.012
Citation  Li D, et al. (2017) Chromatin Accessibility Dynamics during iPSC Reprogramming. Cell Stem Cell 21(6):819-833.e6
abstractText  Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.
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