title: Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.
abstract: Cell type-specific master transcription factors (TFs) play vital roles in defining cell identity and function. However, the roles ubiquitous factors play in the specification of cell identity remain underappreciated. Here we show that the ubiquitous CCAAT-binding NF-Y complex is required for the maintenance of embryonic stem cell (ESC) identity and is an essential component of the core pluripotency network. Genome-wide studies in ESCs and neurons reveal that NF-Y regulates not only genes with housekeeping functions through cell type-invariant promoter-proximal binding, but also genes required for cell identity by binding to cell type-specific enhancers with master TFs. Mechanistically, NF-Y's distinct DNA-binding mode promotes master/pioneer TF binding at enhancers by facilitating a permissive chromatin conformation. Our studies unearth a conceptually unique function for histone-fold domain (HFD) protein NF-Y in promoting chromatin accessibility and suggest that other HFD proteins with analogous structural and DNA-binding properties may function in similar ways.
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Oldfield
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA; Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Pengyi
authors.initials: P
authors.lastname: Yang
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Conway
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Cinghu
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Freudenberg
authors.affiliation: CR Rao Advanced Institute of Mathematics, Statistics & Computer Science, Hyderabad, Andhra Pradesh 500 046, India.
authors.forename: Sailu
authors.initials: S
authors.lastname: Yellaboina
authors.affiliation: Systems Biology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA; Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: jothi@mail.nih.gov.
authors.forename: Raja
authors.initials: R
authors.lastname: Jothi
mesh_terms: D000818:Animals; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008957:Models, Genetic; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D039904:Pluripotent Stem Cells; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D023081:CCAAT-Binding Factor; D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors