Oral Presentation 40th Annual Lorne Genome Conference 2019

Transient and Permanent Reconfiguration of Chromatin and Transcription Factor Occupancy Drive Reprogramming (#45)

Anja S Knaupp 1 , Sam Buckberry 2 , Jahnvi Pflueger 2 , Sue Mei Lim 1 , Ethan Ford 2 , Michael R Larcombe 1 , Fernando J Rossello 1 , Alex de Mendoza 2 , Sara Alaei 1 , Jaber Firas 1 , Melissa L Holmes 1 , Shalima S Nair 3 , Susan J Clark 3 , Christian M Nefzger 1 , Ryan Lister 2 , Jose M Polo 1
  1. Monash University, Melbourne, VIC, Australia
  2. The University of Western Australia, Perth, WA, Australia
  3. Garvan Institute of Medical Research, Sydney, NSW, Australia

Ectopic expression of the transcription factors Oct4, Klf4, Sox2 and c-Myc forces reprogramming of somatic cells into induced pluripotent stem cells (iPSC). Only a small minority of cells, however, typically transition to pluripotency which has limited our understanding of what defines cells that successfully reprogram. In order to deepen our understanding of the reprogramming process we have characterised the changes that occur across the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of reprogramming intermediates poised to become iPSC. Our data suggest that widespread reconfiguration of chromatin states and transcription factor occupancy occurs early during reprogramming and cells that fail to reprogram partially retain regulatory elements active in their somatic cell state. A second wave of reconfiguration occurs just prior to cells achieving pluripotency during which a majority of the early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. This comprehensive analysis of the molecular changes that occur during reprogramming broadens our understanding of the reprogramming process by providing crucial insights into iPSC generation and sheds light on how transcription factors access and change the chromatin state during cell fate transitions.