ArticleBMC genomics2011
Nuclear receptor HNF4α binding sequences are widespread in Alu repeats.
Article in BMC genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.Frontiers in endocrinology · 2023Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Corticosterone dynamically regulates retrotransposable element expression in the rat hippocampus and C6 cells.Neurobiology of stress · 2021Article
- Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease.Molecular metabolism · 2021Review
- Human pluripotent reprogramming with CRISPR activators.Nature communications · 2018Article
- Combined sense-antisense Alu elements activate the EGFP reporter gene when stable transfection.Molecular genetics and genomics : MGG · 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
- Evolution of transcription factor binding in metazoans - mechanisms and functional implications.Nature reviews. Genetics · 2014Review
- Protein-DNA binding: complexities and multi-protein codes.Nucleic acids research · 2014Review
- Dynamic Alu methylation during normal development, aging, and tumorigenesis.BioMed research international · 2014Review
- Latent regulatory potential of human-specific repetitive elements.Molecular cell · 2013Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundAlu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression.
resultsHere, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4α, NR2A1), are highly prevalent in Alu repeats. We employ high throughput protein binding microarrays (PBMs) to show that HNF4α binds > 66 unique sequences in Alu repeats that are present in ~1.2 million locations in the human genome. We use chromatin immunoprecipitation (ChIP) to demonstrate that HNF4α binds Alu elements in the promoters of target genes (ABCC3, APOA4, APOM, ATPIF1, CANX, FEMT1A, GSTM4, IL32, IP6K2, PRLR, PRODH2, SOCS2, TTR) and luciferase assays to show that at least some of those Alu elements can modulate HNF4α-mediated transactivation in vivo (APOM, PRODH2, TTR, APOA4). HNF4α-Alu elements are enriched in promoters of genes involved in RNA processing and a sizeable fraction are in regions of accessible chromatin. Comparative genomics analysis suggests that there may have been a gain in HNF4α binding sites in Alu elements during evolution and that non Alu repeats, such as Tiggers, also contain HNF4α sites.
conclusionsOur findings suggest that HNF4α, in addition to regulating gene expression via high affinity binding sites, may also modulate transcription via low affinity sites in Alu repeats.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.