title: Enterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B(0)AT1) by transcriptional and epigenetic networks.
abstract: Enterocytes are specialized to absorb nutrients from the lumen of the small intestine by expressing a select set of genes to maximize the uptake of nutrients. They develop from stem cells in the crypt and differentiate into mature enterocytes while moving along the crypt-villus axis. Using the Slc6a19 gene as an example, encoding the neutral amino acid transporter B(0)AT1, we studied regulation of the gene by transcription factors and epigenetic factors in the intestine. To investigate this question, we used a fractionation method to separate mature enterocytes from crypt cells and analyzed gene expression. Transcription factors HNF1a and HNF4a activate transcription of the Slc6a19 gene in villus enterocytes, whereas high levels of SOX9 repress expression in the crypts. CpG dinucleotides in the proximal promoter were highly methylated in the crypt and fully de-methylated in the villus. Furthermore, histone modification H3K27Ac, indicating an active promoter, was prevalent in villus cells but barely detectable in crypt cells. The results suggest that Slc6a19 expression in the intestine is regulated at three different levels involving promoter methylation, histone modification, and opposing transcription factors.
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: Emrah
authors.initials: E
authors.lastname: Tümer
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bröer
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: Sarojini
authors.initials: S
authors.lastname: Balkrishna
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: Torsten
authors.initials: T
authors.lastname: Jülich
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia. Electronic address: Stefan.broeer@anu.edu.au.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation / Q000502:physiology; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D006657:Histones; C496488:Hnf1a protein, mouse; C496593:Hnf4a protein, mouse; C505021:SLC6A19 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse
keywords: Amino Acid Transport; DNA Methylation; Epithelial Cell; HNF-4; Histone Modification; Promoters; Transcription Regulation