title: PU.1 and C/EBP(alpha) synergistically program distinct response to NF-kappaB activation through establishing monocyte specific enhancers.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92037, USA.
authors.forename: Fulai
authors.initials: F
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.forename: Rama
authors.initials: R
authors.lastname: Natarajan
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D006657:Histones; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D050880:p300-CBP Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C515848:CEBPA protein, human