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

Date

2017

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.

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Journal article

Citation

Cell Stem Cell, 2017; 21(6):834-845

Statement of Responsibility

Anja S. Knaupp, Sam Buckberry, Jahnvi Pflueger, Sue Mei Lim, Ethan Ford, Michael R. Larcombe, Fernando J. Rossello, Alex de Mendoza, Sara Alaei, Jaber Firas, Melissa L. Holmes, Shalima S. Nair, Susan J. Clark, Christian M. Nefzger, Ryan Lister, Jose M. Polo

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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.

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© 2017 Elsevier Inc.

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