Enterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B(0)AT1) by transcriptional and epigenetic networks.

Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE

Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology

Amino Acid Transport Systems, Neutral/*biosynthesis ; Enterocytes/*metabolism ; Epigenesis, Genetic/*physiology ; Hepatocyte Nuclear Factor 1-alpha/*metabolism ; Hepatocyte Nuclear Factor 4/*metabolism ; Promoter Regions, Genetic/*physiology ; SOX9 Transcription Factor/*metabolism ; Transcription, Genetic/*physiology; Amino Acid Transport Systems, Neutral/genetics ; Animals ; Cells, Cultured ; DNA Methylation/physiology ; Enterocytes/cytology ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Hepatocyte Nuclear Factor 4/genetics ; Histones/genetics ; Histones/metabolism ; Mice ; Protein Processing, Post-Translational/physiology ; SOX9 Transcription Factor/genetics

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.

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Keywords: Amino Acid Transport; DNA Methylation; Epithelial Cell; HNF-4; Histone Modification; Promoters; Transcription Regulation

0 (Amino Acid Transport Systems, Neutral)
0 (Hepatocyte Nuclear Factor 1-alpha)
0 (Hepatocyte Nuclear Factor 4)
0 (Histones)
0 (Hnf1a protein, mouse)
0 (Hnf4a protein, mouse)
0 (SLC6A19 protein, mouse)
0 (SOX9 Transcription Factor)
0 (Sox9 protein, mouse)

Date Created: 20131015 Date Completed: 20140204 Latest Revision: 20211021

20240829

PMC3837124

10.1074/jbc.M113.482760

24121511