ArticleAmerican journal of physiology. Cell physiology2013
Regulation of intestinal serotonin transporter expression via epigenetic mechanisms: role of HDAC2.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome.Molecular metabolism · 2020Trial
- A Novel Epigenetic Mechanism of Intestinal NHE3 Gene Regulation by Histone Acetylation.International journal of molecular sciences · 2026Article
- Crosstalk Between Gut Microbiota, Epigenome, and Neurotransmitters in Health and Disease.Cells · 2026Review
- Microbial short chain fatty acids: Effective histone deacetylase inhibitors in immune regulation (Review).International journal of molecular medicine · 2026Review
- The Influence of BMP6 on Serotonin and Glucose Metabolism.International journal of molecular sciences · 2024Article
- New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics.Journal of gastroenterology · 2023Review
- Sensory Processing Sensitivity and Gastrointestinal Symptoms in Japanese Adults.International journal of environmental research and public health · 2022Article
- Mucosal Serotonin Reuptake Transporter Expression in Irritable Bowel Syndrome Is Modulated by Gut Microbiota Via Mast Cell-Prostaglandin E2.Gastroenterology · 2022Article
- Article
- Connecting gut microbiomes and short chain fatty acids with the serotonergic system and behavior inFrontiers in physiology · 2022Review
- Histone deacetylase inhibitors regulate vitamin C transporter functional expression in intestinal epithelial cells.The Journal of nutritional biochemistry · 2021Article
- Histone Deacetylases in the Inflamed Intestinal Epithelium-Promises of New Therapeutic Strategies.Frontiers in medicine · 2021Review
- Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells.American journal of physiology. Cell physiology · 2020Article
- Effects of Thryptophan Hydroxylase Blockade by P-Chlorophenylalanine on Contextual Memory Reconsolidation after Training of Different Intensity.International journal of molecular sciences · 2020Article
- Serotonin transporter untranslated regions influence mRNA abundance and protein expression.Gene reports · 2020Article
- Analysis of gut microbiota of obese individuals with type 2 diabetes and healthy individuals.PloS one · 2019Article
- Multifaceted Regulations of the Serotonin Transporter: Impact on Antidepressant Response.Frontiers in neuroscience · 2019Review
- SRARP and HSPB7 are epigenetically regulated gene pairs that function as tumor suppressors and predict clinical outcome in malignancies.Molecular oncology · 2018Article
- Looking Beyond the 5-HTTLPR Polymorphism: Genetic and Epigenetic Layers of Regulation Affecting the Serotonin Transporter Gene Expression.Molecular neurobiology · 2017Review
- Serotonin Transporter Genotype Modulates the Gut Microbiota Composition in Young Rats, an Effect Augmented by Early Life Stress.Frontiers in cellular neuroscience · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin (5-HT) transporter (SERT) facilitates clearance of extracellular 5-HT by its uptake and internalization. Decreased expression of SERT and consequent high 5-HT levels have been implicated in various diarrheal disorders. Thus, appropriate regulation of SERT is critical for maintenance of 5-HT homeostasis in health and disease. Previous studies demonstrated that SERT is regulated via posttranslational and transcriptional mechanisms. However, the role of epigenetic mechanisms in SERT regulation is not known. Current studies investigated the effects of histone deacetylase (HDAC) inhibition on SERT expression and delineated the mechanisms. Treatment of Caco-2 cells with the pan-HDAC inhibitors butyrate (5 mM) and trichostatin (TSA, 1 μM) decreased SERT mRNA and protein levels. Butyrate- or TSA-induced decrease in SERT was associated with decreased activity of human SERT (hSERT) promoter 1 (upstream of exon 1a), but not hSERT promoter 2 (upstream of exon 2). Butyrate + TSA did not show an additive effect on SERT expression, indicating that mechanisms involving histone hyperacetylation may be involved. Chromatin immunoprecipitation assays demonstrated enrichment of the hSERT promoter 1 (flanking nt -250/+2) with tetra-acetylated histone H3 or H4, which was increased (~3-fold) by butyrate. Interestingly, specific inhibition of HDAC2 (but not HDAC1) utilizing small interfering RNA decreased SERT mRNA and protein levels. The decrease in SERT expression by HDAC inhibition was recapitulated in an in vivo model. SERT mRNA levels were decreased in the ileum and colon of mice fed pectin (increased availability of butyrate) compared with controls fed a fiber-free diet (~50-60%). Our results identify a novel role of HDAC2 as a regulator of SERT gene expression in intestinal epithelial cells.
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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.