ArticlePloS one2011
A high resolution genome-wide scan of HNF4α recognition sites infers a regulatory gene network in colon cancer.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Predicting the impact of sequence motifs on gene regulation using single-cell data.Genome biology · 2023Article
- Urate transport in health and disease.Best practice & research. Clinical rheumatology · 2021Review
- Sex Differences in Urate Handling.International journal of molecular sciences · 2020Review
- Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of theHaematologica · 2019Article
- Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.Reproductive biology and endocrinology : RB&E · 2018Article
- In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP.Scientific reports · 2017Article
- Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.Molecular and cellular biology · 2015Article
- Regulation of Liver Enriched Transcription Factors in Rat Hepatocytes Cultures on Collagen and EHS Sarcoma Matrices.PloS one · 2015Article
- Large differences in global transcriptional regulatory programs of normal and tumor colon cells.BMC cancer · 2014Article
- Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.Genome biology · 2014Article
- Orphan nuclear receptor HNF4G promotes bladder cancer growth and invasion through the regulation of the hyaluronan synthase 2 gene.Oncogenesis · 2013Article
- HNF4α: a new biomarker in colon cancer?Biomarkers in medicine · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatic nuclear factor HNF4α is a versatile transcription factor and controls expression of many genes in development, metabolism and disease. To delineate its regulatory gene network in colon cancer and to define novel gene targets a comprehensive genome-wide scan was carried out at a resolution of 35 bp with chromatin IP DNA obtained from the human colon carcinoma cell line Caco-2 that is a particularly rich source of HNF4α. More than 90% of HNF4α binding sites were mapped as promoter distal sequences while enhancer elements could be defined to foster chromatin loops for interaction with other promoter-bound transcription factors. Sequence motif analysis by various genetic algorithms evidenced a unique enhanceosome that consisted of the nuclear proteins ERα, AP1, GATA and HNF1α as cooperating transcription factors. Overall >17,500 DNA binding sites were identified with a gene/binding site ratio that differed >6-fold between chromosomes and clustered in distinct chromosomal regions amongst >6600 genes targeted by HNF4α. Evidence is presented for nuclear receptor cross-talk of HNF4α and estrogen receptor α that is recapitulated at the sequence level. Remarkably, the Y-chromosome is devoid of HNF4α binding sites. The functional importance of enrichment sites was confirmed in genome-wide gene expression studies at varying HNF4α protein levels. Taken collectively, a genome-wide scan of HNF4α binding sites is reported to better understand basic mechanisms of transcriptional control of HNF4α targeted genes. Novel promoter distal binding sites are identified which form an enhanceosome thereby facilitating RNA processing events.
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