ArticlePLoS genetics2012
Intronic cis-regulatory modules mediate tissue-specific and microbial control of angptl4/fiaf transcription.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
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- Directly Measuring Atherogenic Lipoprotein Kinetics in Zebrafish With the Photoconvertible LipoTimer Reporter.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
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- Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome.bioRxiv : the preprint server for biology · 2024Article
- Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics.Advances in experimental medicine and biology · 2024Review
- Fecal Microbiome Analysis Distinguishes Bacterial Taxa Biomarkers Associated with Red Fillet Color in Rainbow Trout.Microorganisms · 2023Article
- Zebrafish: an efficient vertebrate model for understanding role of gut microbiota.Molecular medicine (Cambridge, Mass.) · 2022Review
- Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.Genetics · 2022Article
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- Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2022Article
- Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ.International journal of molecular sciences · 2021Review
- Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium.Nature reviews. Gastroenterology & hepatology · 2021Review
- Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine.Genomics, proteomics & bioinformatics · 2020Article
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- Commensal microbiota modulate gene expression in the skin.Microbiome · 2018Article
- Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.PLoS biology · 2017Article
- Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha.Genome research · 2017Article
- Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.Scientific reports · 2017Article
- Article
- Best practices for germ-free derivation and gnotobiotic zebrafish husbandry.Methods in cell biology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis-regulatory mechanisms underlying intestine-specific and microbial control of Angptl4 transcription, we utilized the zebrafish system in which host regulatory DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate. We found that zebrafish angptl4 is transcribed in multiple tissues including the liver, pancreatic islet, and intestinal epithelium, which is similar to its mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the intestinal epithelium upon colonization with a microbiota. In vivo transgenic reporter assays identified discrete tissue-specific regulatory modules within angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet β-cells, or intestinal enterocytes. Comparative sequence analyses and heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish species revealed differential evolution of the islet and intestinal regulatory modules. High-resolution functional mapping and site-directed mutagenesis defined the minimal set of regulatory sequences required for intestinal activity. Strikingly, the microbiota suppressed the transcriptional activity of the intestine-specific regulatory module similar to the endogenous angptl4 gene. These results suggest that the microbiota might regulate host intestinal Angptl4 protein expression and peripheral fat storage by suppressing the activity of an intestine-specific transcriptional enhancer. This study provides a useful paradigm for understanding how microbial signals interact with tissue-specific regulatory networks to control the activity and evolution of host gene transcription.
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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.