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https://hdl.handle.net/2440/133704
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Type: | Journal article |
Title: | Transient and Permanent Reconfiguration of Chromatin and Transcription Factor Occupancy Drive Reprogramming |
Author: | 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. |
Citation: | Cell Stem Cell, 2017; 21(6):834-845 |
Publisher: | Elsevier |
Issue Date: | 2017 |
ISSN: | 1934-5909 1875-9777 |
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 |
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. |
Keywords: | ATAC-sequencing; ChIP-sequencing; DNA methylation; reprogramming intermediates; refractory cells; induced pluripotent stem cells; Oct4; Sox2; chromatin remodeling; transcriptional waves |
Rights: | © 2017 Elsevier Inc. |
DOI: | 10.1016/j.stem.2017.11.007 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1069830 http://purl.org/au-research/grants/arc/CE140100008 http://purl.org/au-research/grants/nhmrc/1036587 http://purl.org/au-research/grants/arc/FT120100862 http://purl.org/au-research/grants/nhmrc/1111206 http://purl.org/au-research/grants/nhmrc/1092280 |
Published version: | http://dx.doi.org/10.1016/j.stem.2017.11.007 |
Appears in Collections: | Medical Sciences publications |
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