ArticleThe Journal of biological chemistry2011
Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Tristetraprolin attenuates schistosomiasis-induced liver fibrosis through m⁶A-mediated regulation of TGF-β1 mRNA stability.PLoS pathogens · 2026Article
- [Inhibiting Yes-associated protein alleviates CClNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Analysis of the DNA-binding properties of TGF-β-activated Smad complexes unveils a possible molecular basis for cellular context-dependent signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes.Journal of biochemistry · 2022Article
- Ccn2a is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish.Development (Cambridge, England) · 2021Article
- Gene expression profiles of liver cancer cell lines reveal two hepatocyte-like and fibroblast-like clusters.PloS one · 2021Article
- A Comprehensive Genomic Analysis Constructs miRNA-mRNA Interaction Network in Hepatoblastoma.Frontiers in cell and developmental biology · 2021Article
- A hierarchical network of hypoxia-inducible factor and SMAD proteins governs procollagen lysyl hydroxylase 2 induction by hypoxia and transforming growth factor β1.The Journal of biological chemistry · 2019Article
- Venous identity requires BMP signalling through ALK3.Nature communications · 2019Article
- The role of contextual signal TGF-β1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases: an update on its pathological significance and therapeutic potential.Contemporary oncology (Poznan, Poland) · 2019Review
- Intracellular and extracellular TGF-β signaling in cancer: some recent topics.Frontiers of medicine · 2018Review
- Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.British journal of pharmacology · 2018Article
- Reactive oxygen species modulator 1 regulates oxidative stress and induces renal and pulmonary fibrosis in a unilateral ureteral obstruction rat model and in HK‑2 cells.Molecular medicine reports · 2017Article
- TGF-β inhibits IL-7-induced proliferation in memory but not naive human CD4Journal of leukocyte biology · 2017Article
- A strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells.Developmental biology · 2016Review
- Transcriptional Control by the SMADs.Cold Spring Harbor perspectives in biology · 2016Review
- Understanding kidney morphogenesis to guide renal tissue regeneration.Nature reviews. Nephrology · 2016Review
- RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.Oncogene · 2016Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.Oncogene · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 this study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and we compared them with 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. Chromatin immunoprecipitation sequencing analysis of HNF4α binding regions under TGF-β 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.
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