PU.1 and C/EBPalpha synergistically program distinct response to NF-kappaB activation through establishing monocyte-specific enhancers
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE26994
PROVIDER: PRJNA136935 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. Using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-kappaB signaling pathway. We showed that, after tumor necrosis factor-alpha (TNF-alpha) treatment, NF-kappaB 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 pre-existing cell-type specific enhancers prior to TNF-alpha stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPalpha, appear to synergistically mediate enhancer creation and affect NF-kappaB target selection in THP-1 cells. In HeLa cells, co-expression of PU.1 and C/EBPalpha conferred TNF-alpha responsiveness to a subset of THP-1 specific NF-kappaB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from pre-existing enhancers that are established by cell specific transcription factors. We used Affymetrix microarray (GPL570) to obtain gene expression data for THP1 and HeLa cells before and after TNF-alpha treatment.
2011-03-15 | E-GEOD-26868 | biostudies-arrayexpress
Project description:Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. Using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-kappaB signaling pathway. We showed that, after tumor necrosis factor-alpha (TNF-alpha) treatment, NF-kappaB 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 pre-existing cell-type specific enhancers prior to TNF-alpha stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPalpha, appear to synergistically mediate enhancer creation and affect NF-kappaB target selection in THP-1 cells. In HeLa cells, co-expression of PU.1 and C/EBPalpha conferred TNF-alpha responsiveness to a subset of THP-1 specific NF-kappaB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from pre-existing enhancers that are established by cell specific transcription factors.
2011-03-15 | GSE26868 | GEO
Project description:Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. Using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-kappaB signaling pathway. We showed that, after tumor necrosis factor-alpha (TNF-alpha) treatment, NF-kappaB 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 pre-existing cell-type specific enhancers prior to TNF-alpha stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPalpha, appear to synergistically mediate enhancer creation and affect NF-kappaB target selection in THP-1 cells. In HeLa cells, co-expression of PU.1 and C/EBPalpha conferred TNF-alpha responsiveness to a subset of THP-1 specific NF-kappaB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from pre-existing enhancers that are established by cell-specific transcription factors.
2011-03-15 | GSE26988 | GEO
Project description: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.
| S-EPMC3069155 | biostudies-literature
Project description:PU.1 and C/EBPalpha synergistically program distinct response to NF-kappaB activation through establishing monocyte specific enhancers (expression data)
| PRJNA142011 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-03-15 | GSE26994 | GEO
Project description:PU.1 and C/EBPalpha synergistically program distinct response to NF-kappaB activation through establishing monocyte-specific enhancers (ChIP-chip data)
| PRJNA142033 | ENA
Project description:We examined genome-wide variation in transcription factor binding in different individuals and a chimpanzee using chromatin immunoprecipitation followed by massively-parallel sequencing (ChIP-Seq). The binding sites of RNA Polymerase II (Pol II) as well as a key regulator of immune responses, NFkB, were mapped in ten HapMap lymphoblastoid cell lines derived from individuals of African, European, and Asian ancestry, including a parent-offspring trio. We also mapped gene expression in all ten human cell lines for two treatment conditions: a) no treatment and b) following induction by TNF-alpha. Genome-wide comparison of Pol II and NF-KappaB binding in ten individuals. ChIP-seq with NF-KappaB.
2010-03-22 | E-GEOD-19485 | biostudies-arrayexpress
Project description:In the central nervous system (CNS) the transcription factor NF-kappaB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-kappaB-dependent genes is activated, leading to both protective and detrimental effects on CNS recovery. Here we show that transgenic inactivation of astroglial NF-kappaB in mice (GFAP-IkappaBalpha-dn mice) resulted in dramatic reduction of disease severity and improvement in functional recovery following EAE. This coincided with a higher presence of leukocytes in the cord and brain of transgenic mice at the chronic phase of the disease, when the functional recovery over WT mice was the most significant. We observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, while the loss of neuronal-specific molecules essential for synaptic transmission was limited compared to WT mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-kappaB in astrocytes results in neuroprotective effects following EAE, directly implicating astrocytes in the pathophysiology of this disease. Keywords: time course, EAE, transgenic mice, astrocytes, inflammation, cytokines, chemokines
2009-01-01 | GSE10235 | GEO
Project description:The transcription factor NF-kappaB is constitutively activated in many epithelial tumors but few NF-kappaB inhibitors are suitable for cancer therapy because of the broad biological effects of NF-κB. We previously reported that the d4 family (DPF1, DPF2, DPF3a/b) function as adaptor proteins linking NF-kappaB with the SWI/SNF complex. Here, we demonstrate that in epithelial tumor cell lines, exogenous expression of the highly conserved N-terminal 84-amino acid region of either DPF2 or DPF3a/b (designated “CT1”) has stronger inhibitory effects on anchorage-independent growth than single knockdown of any d4 protein, indicating that CT1 can function as an efficient dominant-negative mutant of the entire d4 family. By proximity ligation assays, CT1 was further shown to retain full function as an adaptor. Microarray analysis categorized NF-kappaB target genes by their CT1 sensitivity. Among CT1-sensitive genes, IL-6 was shown to strongly contribute to the anchorage-independent growth. Finally, exogenous CT1 expression efficiently suppressed tumor formation in a mouse xenograft model, suggesting that the d4 protein family could be a promising cancer therapy target.
2017-09-22 | GSE93768 | GEO