Histone-Fold Domain Protein NF-Y Promotes Chromatin Accessibility for Cell Type-Specific Master Transcription Factors

被引：146

作者：

Oldfield, Andrew J. ^{[1
]}

Yang, Pengyi ^{[1
,2
]}

Conway, Amanda E. ^{[1
]}

Cinghu, Senthilkumar ^{[1
]}

Freudenberg, Johannes M. ^{[1
]}

Yellaboina, Sailu ^{[3
]}

Jothi, Raja ^{[1
,2
]}

机构：

[1] NIEHS, Syst Biol Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA

[2] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA

[3] CR Rao Adv Inst Math Stat & Comp Sci, Hyderabad 500046, Andhra Pradesh, India

来源：

MOLECULAR CELL | 2014年 / 55卷 / 05期

关键词：

EMBRYONIC STEM-CELLS; DNA BINDING-SITES; CHIP-SEQ DATA; CBF/NF-Y; FACILITATES PLURIPOTENCY; GENES; GENOME; MOUSE; IDENTIFICATION; ACTIVATION;

D O I：

10.1016/j.molcel.2014.07.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 stemcell (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.

引用

页码：708 / 722

页数：15