@article{14a9a64b605d4c5d9faad35e190ec2c9,
title = "Dynamic regulation of chromatin accessibility by pluripotency transcription factors across the cell cycle",
abstract = "The pioneer activity of transcription factors allows for opening of inaccessible regulatory elements and has been extensively studied in the context of cellular differentiation and reprogramming. In contrast, the function of pioneer activity in self-renewing cell divisions and across the cell cycle is poorly understood. Here we assessed the interplay between OCT4 and SOX2 in controlling chromatin accessibility of mouse embryonic stem cells. We found that OCT4 and SOX2 operate in a largely independent manner even at co-occupied sites, and that their cooperative binding is mostly mediated indirectly through regulation of chromatin accessibility. Controlled protein degradation strategies revealed that the uninterrupted presence of OCT4 is required for post-mitotic re-establishment and interphase maintenance of chromatin accessibility, and that highly OCT4-bound enhancers are particularly vulnerable to transient loss of OCT4 expression. Our study sheds light on the constant pioneer activity required to maintain the dynamic pluripotency regulatory landscape in an accessible state.",
author = "Friman, {Elias T.} and C{\'e}dric Deluz and Meireles-Filho, {Antonio C.A.} and Subashika Govindan and Vincent Gardeux and Bart Deplancke and Suter, {David M.}",
note = "Funding Information: This work was supported by the Swiss National Science Foundation (grants #PP00P3_179068 and PP00P3_17205 to DMS). ACAMF was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme. This work was further supported by AgingX (SystemsX.ch) and SNF (310030_182655). We thank Bastien Mangeat, Elisa Cora, Paolo Ferrari, and Lionel Ponsonnet from the Gene Expression Core Facility for high-throughput sequencing, Miguel Garcia, Lo?c Tauzin, Val?rie Glutz, and Andr? Mozes from the Flow Cytometry Core Facility for cell sorting, Olivier Burri and Romain Guiet from the Bioimaging and Optics Platform for assistance with cell tracking, the staff at Vital-IT and SCITAS for cluster computing, and Armelle Tollenaere for critical reading of the manuscript. Funding Information: This work was supported by the Swiss National Science Foundation (grants #PP00P3_179068 and PP00P3_17205 to DMS). ACAMF was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme. This work was further supported by AgingX (SystemsX.ch) and SNF (310030_182655). We thank Bastien Mangeat, Elisa Cora, Paolo Ferrari, and Lionel Ponsonnet from the Gene Expression Core Facility for high-throughput sequencing, Miguel Garcia, Lo{\"i}c Tauzin, Val{\'e}rie Glutz, and Andr{\'e} Mozes from the Flow Cytometry Core Facility for cell sorting, Olivier Burri and Romain Guiet from the Bioimaging and Optics Platform for assistance with cell tracking, the staff at Vital-IT and SCITAS for cluster computing, and Armelle Tollenaere for critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2019, eLife Sciences Publications Ltd. All rights reserved.",
year = "2019",
month = dec,
doi = "10.7554/eLife.50087",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}