title: The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells.
abstract: Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming. During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this. Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells. Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 to support additional transcription factor binding and expression of the pluripotency-associated transcriptome. Furthermore, the requirement for BRG1 in shaping OCT4 binding reflects how these target sites are used during cellular reprogramming and early mouse development. Together this reveals a distinct requirement for a chromatin remodeller in promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Hamish W
authors.identifier: http://orcid.org/0000-0001-5972-8926
authors.initials: HW
authors.lastname: King
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Robert J
authors.identifier: http://orcid.org/0000-0002-8726-7888
authors.initials: RJ
authors.lastname: Klose
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors; D004247:DNA; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: chromatin accessibility; chromatin remodeller; chromosomes; developmental biology; embryonic stem cells; gene regulation; genes; mouse; pioneer factor; pluripotency; stem cells