Open AccessPU.1 and C/EBPα synergistically program distinct response to NF-κB activation through establishing monocyte specific enhancers
Author(s) -
Fulai Jin,
Yán Li,
Bing Ren,
Rama Natarajan
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1017214108
Subject(s) - enhancer , transcription factor , hela , biology , cell type , transcription (linguistics) , microbiology and biotechnology , cell , gene , nfkb1 , epigenetics , genetics , linguistics , philosophy
Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. By using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-κB signaling pathway. We showed that, after TNF-α treatment, the NF-κB p65 subunit binds to distinct genome locations and subsequently induces different subsets of genes in human monocytic THP-1 cells versus HeLa cells. Interestingly, the differential p65 binding in two cell types correlates with preexisting cell type-specific enhancers before TNF-α stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPα, appear to synergistically mediate enhancer creation and affect NF-κB target selection in THP-1 cells. In HeLa cells, coexpression of PU.1 and C/EBPα conferred TNF-α responsiveness to a subset of THP-1–specific NF-κB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from preexisting enhancers that are established by cell-specific transcription factors.