Unknown,Transcriptomics,Genomics,Proteomics

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Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors [ChIP-seq]


ABSTRACT: Cell type-specific master transcription factors (MTFs) 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 all three subunits of the ubiquitous heterotrimeric CCAAT-binding NF-Y complex are required for the maintenance of embryonic stem cell (ESC) identity, and establish NF-Y as a novel component of the core pluripotency network. Genome-wide occupancy and transcriptomic analyses in ESCs and neurons reveal that not only does NF-Y regulate 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 MTFs. Mechanistically, NF-Y's distinctive DNA-binding mode promotes MTF binding at enhancers by facilitating a permissive chromatin conformation. Our studies unearth a novel function for NF-Y in promoting chromatin accessibility, and suggest that other proteins with analogous structural and DNA-binding properties may function in similar ways. Genome-wide mapping of NF-YA, NF-YB, and NF-YC subunits of the NF-Y complex in mouse ESCs, and microarray gene expression profiling of control knockdown (KD), NF-YA KD, NF-YB KD, NF-YC KD, and NF-YA/NF-YB/NF-YC triple KD ESCs.

ORGANISM(S): Mus musculus

SUBMITTER: Raja Jothi 

PROVIDER: E-GEOD-56839 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.

Oldfield Andrew J AJ   Yang Pengyi P   Conway Amanda E AE   Cinghu Senthilkumar S   Freudenberg Johannes M JM   Yellaboina Sailu S   Jothi Raja R  

Molecular cell 20140814 5


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 ho  ...[more]

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