Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA106007 | ENA |
REPOSITORIES: ENA
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Project description:Specific regulation of target genes by transforming growth factor-β (TGF-β) in a given cellular context is determined in part by transcription factors and cofactors that interact with the Smad complex. In the present study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and compared them to those in HaCaT epidermal keratinocytes to elucidate the mechanisms of cell type- and context-dependent regulation of transcription induced by TGF-β. Our results show that 81% of the Smad2/3 binding regions in HepG2 cells were not shared with those found in HaCaT cells. Hepatocyte nuclear factor 4α (HNF4α) is expressed in HepG2 cells, but not in HaCaT cells, and the HNF4α binding motif was identified as an enriched motif in the HepG2-specific Smad2/3 binding regions. ChIP-sequencing analysis of HNF4A binding regions under TGF-β stimulation revealed that 32.5% of the Smad2/3 binding regions overlapped HNF4A bindings. MIXL1 was identified as a new combinatorial target of HNF4A and Smad2/3, and both the HNF4A protein and its binding motif were required for the induction of MIXL1 by TGF-β in HepG2 cells. These findings generalize the importance of binding of HNF4A on Smad2/3 binding genomic regions for HepG2-specific regulation of transcription by TGF-β, and suggest that certain transcription factors expressed in a cell-type-specific manner play important roles in the transcription regulated by the TGF-β-Smad signaling pathway. HepG2 cells were treated with TGF-beta for 1.5 h or left untreated. anti-HNF4A ChIP-seq was performed. One lane was used for each sample.
2011-06-08 | E-GEOD-28845 | biostudies-arrayexpress
Project description:Specific regulation of target genes by transforming growth factor-β (TGF-β) in a given cellular context is determined in part by transcription factors and cofactors that interact with the Smad complex. In the present study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and compared them to those in HaCaT epidermal keratinocytes to elucidate the mechanisms of cell type- and context-dependent regulation of transcription induced by TGF-β. Our results show that 81% of the Smad2/3 binding regions in HepG2 cells were not shared with those found in HaCaT cells. Hepatocyte nuclear factor 4α (HNF4α) is expressed in HepG2 cells, but not in HaCaT cells, and the HNF4α binding motif was identified as an enriched motif in the HepG2-specific Smad2/3 binding regions. ChIP-sequencing analysis of HNF4A binding regions under TGF-β stimulation revealed that 32.5% of the Smad2/3 binding regions overlapped HNF4A bindings. MIXL1 was identified as a new combinatorial target of HNF4A and Smad2/3, and both the HNF4A protein and its binding motif were required for the induction of MIXL1 by TGF-β in HepG2 cells. These findings generalize the importance of binding of HNF4A on Smad2/3 binding genomic regions for HepG2-specific regulation of transcription by TGF-β, and suggest that certain transcription factors expressed in a cell-type-specific manner play important roles in the transcription regulated by the TGF-β-Smad signaling pathway.
2011-06-08 | GSE28845 | GEO
Project description:Specific regulation of target genes by transforming growth factor-β (TGF-β) in a given cellular context is determined in part by transcription factors and cofactors that interact with the Smad complex. In the present study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and compared them to those in HaCaT epidermal keratinocytes to elucidate the mechanisms of cell-type- and context-dependent regulation of transcription induced by TGF-β. Our results show that 81% of the Smad2/3 binding regions in HepG2 cells were not shared with those found in HaCaT cells. Hepatocyte nuclear factor 4α (HNF4α) is expressed in HepG2 cells, but not in HaCaT cells, and the HNF4α binding motif was identified as an enriched motif in the HepG2-specific Smad2/3 binding regions. ChIP-sequencing analysis of HNF4α binding regions under TGFα stimulation revealed that 32.5% of the Smad2/3 binding regions overlapped HNF4α bindings. MIXL1 was identified as a new combinatorial target of HNF4α and Smad2/3, and both the HNF4α protein and its binding motif were required for the induction of MIXL1 by TGF-β in HepG2 cells. These findings generalize the importance of binding of HNF4α on Smad2/3 binding genomic regions for HepG2-specific regulation of transcription by TGF-β, and suggest that certain transcription factors expressed in a cell-type-specific manner play important roles in the transcription regulated by the TGF-β-Smad signaling pathway.
2011-06-08 | GSE28797 | GEO
Project description:Smad2/3 are transcription factors that engage in TGF-beta-induced transcription. Here we analyzed the effect of identified Smad2/3 binding sites to transcription. We used expression microarrays to compare the Smad2/3 binding sites identified by ChIP-chip to TGF-beta-induced gene expressions. Keywords: time course We also examined the effect of either ETS1/TFAP2A/SMAD2/SMAD3 siRNAs on TGF-beta-induced gene expression change.
2008-10-29 | GSE11710 | GEO
Project description:Smad2/3 are transcription factors that engage in TGF-beta-induced transcription. We determined and analyzed HepG2 and Hep3B-specific Smad2/3 binding sites by ChIP-chip. We used expression microarrays to compare the Smad2/3 and HNF4alpha binding sites identified by ChIP-chip or ChIP-seq, respectively, to TGF-beta-induced gene expressions. HepG2 cells were transfected with control or HNF4A siRNAs and treated with 3 ng/ml TGF-beta for 0, 1.5 and 24 h (6 samples in total, no replicates). Total RNA was extracted and expression microarray analysis was performed as described in the protocols.
2011-06-08 | E-GEOD-28590 | biostudies-arrayexpress
Project description:Smad2/3 are transcription factors that engage in TGF-beta-induced transcription. We determined and analyzed HepG2 and Hep3B-specific Smad2/3 binding sites by ChIP-chip. We used expression microarrays to compare the Smad2/3 and HNF4alpha binding sites identified by ChIP-chip or ChIP-seq, respectively, to TGF-beta-induced gene expressions.
2011-06-08 | GSE28590 | GEO
Project description:Transforming growth factor (TGF)-beta induces apoptosis of many types of cancer cells and acts as a tumor suppressor. We found lower expression of TGF-beta type II receptor (TbRII) in most of SCLC cells and tissues than in normal lung epithelial cells and normal lung tissues, respectively. In vitro cell growth and in vivo tumor formation were suppressed by TGF-beta-mediated apoptosis when the wild-type TbRII was overexpressed in SCLC cells. We therefore determined Smad2 and Smad3 (Smad2/3) binding sites in a SCLC cell line H345 stably expressing exogenous TbRII (H345-TbRII) to identify target genes of TGF-beta. Smad2 and Smad3 binding sites in H345-TbRII cells were determined by ChIP-seq (one sample analysis, without replicates).
2015-09-15 | E-GEOD-63871 | biostudies-arrayexpress
Project description:Transforming growth factor (TGF)-beta induces apoptosis of many types of cancer cells and acts as a tumor suppressor. We found lower expression of TGF-beta type II receptor (TbRII) in most of SCLC cells and tissues than in normal lung epithelial cells and normal lung tissues, respectively. In vitro cell growth and in vivo tumor formation were suppressed by TGF-beta-mediated apoptosis when the wild-type TbRII was overexpressed in SCLC cells. We therefore determined Smad2 and Smad3 (Smad2/3) binding sites in a SCLC cell line H345 stably expressing exogenous TbRII (H345-TbRII) to identify target genes of TGF-beta.
2015-09-15 | GSE63871 | GEO
Project description:Smad2 and Smad3 (Smad2/3) primarily mediates the transforming growth factor-β (TGF-β) signaling that drives cell proliferation, differentiation, and migration. The dynamics of the Smad2/3 phosphorylation provides the key mechanism for regulating the TGF-β signaling pathway. Here we identified NLK as a novel regulator of TGF-β signaling pathway via modulating the phosphorylation of Smad2/3 in the linker region.
2021-09-10 | PXD023957 | Pride
Project description:Smad family proteins transduce signals downstream of transforming growth factor-beta (TGF-beta) and are one of the factors that regulate target genes related to diseases affecting the skin. We here identified C2orf54, officially known as MAB21L4, as one of the most up-regulated targets of TGF-beta and Smad3 in a differentiated human progenitor epidermal keratinocyte, using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). Smad2 and Smad3 bind to the regulatory regions of the C2orf54 gene locus. We found that TGF-beta induced expression of a barrier protein involucrin (encoded by IVL gene), and transcriptional activity of the IVL promoter induced by TGF-beta was inhibited by siRNAs for C2orf54. Further analysis revealed that C2orf54 siRNAs also down-regulated the expression of several target genes of TGF-beta. C2orf54 protein located mainly in the cytosol, physically bound to Smad2 and Smad3, but did not inhibit the binding of Smad2 and Smad3 to the target genomic regions. These findings suggested that TGF-beta-induced C2orf54 up-regulates gene expression induced by Smads, possibly through its physical interaction with Smad proteins.
2021-12-16 | GSE180251 | GEO