Document Detail

PU.1 and C/EBP(alpha) synergistically program distinct response to NF-kappaB activation through establishing monocyte specific enhancers.
MedLine Citation:
PMID:  21402921     Owner:  NLM     Status:  MEDLINE    
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.
Fulai Jin; Yan Li; Bing Ren; Rama Natarajan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-14
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-30     Completed Date:  2011-06-10     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5290-5     Citation Subset:  IM    
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MeSH Terms
CCAAT-Enhancer-Binding Proteins / genetics,  metabolism*
Enhancer Elements, Genetic*
Gene Expression Regulation / drug effects*
HeLa Cells
Histones / metabolism
Monocytes / cytology,  physiology*
NF-kappa B / genetics,  metabolism*
Proto-Oncogene Proteins / genetics,  metabolism*
Signal Transduction / physiology
Trans-Activators / genetics,  metabolism*
Transcription Factors / metabolism
Tumor Necrosis Factor-alpha / pharmacology*
p300-CBP Transcription Factors / metabolism
Grant Support
R01 HL087864/HL/NHLBI NIH HHS; R01 HL087864/HL/NHLBI NIH HHS; R01 HL087864-05/HL/NHLBI NIH HHS; R01 HL106089/HL/NHLBI NIH HHS; R01 HL106089/HL/NHLBI NIH HHS; R01DK 065073/DK/NIDDK NIH HHS; R33 CA105829/CA/NCI NIH HHS; R33 CA105829-04/CA/NCI NIH HHS; U01 HG003151/HG/NHGRI NIH HHS; U01 HG003151-03S2/HG/NHGRI NIH HHS
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/CEBPA protein, human; 0/Histones; 0/NF-kappa B; 0/Proto-Oncogene Proteins; 0/Trans-Activators; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha; 0/proto-oncogene protein Spi-1; EC Transcription Factors

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