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-?B signaling pathway. We showed that, after TNF-? treatment, the NF-?B 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-? stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBP?, appear to synergistically mediate enhancer creation and affect NF-?B target selection in THP-1 cells. In HeLa cells, coexpression of PU.1 and C/EBP? conferred TNF-? responsiveness to a subset of THP-1-specific NF-?B 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.

SUBMITTER: Jin F 

PROVIDER: S-EPMC3069155 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature