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Transient and Permanent Reconfiguration of Chromatin and Transcription Factor Occupancy Drive Reprogramming

Abstract

Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states. A second wave of reconfiguration occurs just prior to pluripotency acquisition, where a majority of early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. Our comprehensive characterization of reprogramming-associated molecular changes broadens our understanding of this process and sheds light on how TFs access and change the chromatin during cell-fate transitions.

Type Journal
ISBN 1875-9777 (Electronic) 1875-9777 (Linking)
Authors Knaupp, A. S.; Buckberry, S.; Pflueger, J.; Lim, S. M.; Ford, E.; Larcombe, M. R.; Rossello, F. J.; de Mendoza, A.; Alaei, S.; Firas, J.; Holmes, M. L.; Nair, S. S.; Clark, S. J.; Nefzger, C. M.; Lister, R.; Polo, J. M.
Responsible Garvan Author Prof Susan Clark
Publisher Name Cell Stem Cell
Published Date 2017-12-07
Published Volume 21
Published Issue 6
Published Pages 834-845 e6
Status Published in-print
DOI 10.1016/j.stem.2017.11.007
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29220667