title: AT motif binding factor 1-A (ATBF1-A) negatively regulates transcription of the aminopeptidase N gene in the crypt-villus axis of small intestine.
abstract: This is the first study to demonstrate that the AT motif binding factor 1-A (ATBF1-A) is expressed in the crypts and the bases of villi of the small intestine and negatively regulates transcription of brush-border enzyme gene, aminopeptidase-N (APN). In situ hybridization visualized a limited ATBF1-A mRNA expression in the crypts and the bases of villi. Transient transfection and dual luciferase-reporter assay demonstrated that ATBF1-A suppressed the activity of APN promoter, but did not that of AT motif deleted promoter. These results imply that ATBF1-A inhibits the transcription of APN gene through its direct binding to the AT motif element. Furthermore, butyrate-induced differentiation of Caco-2 cells, retaining the enterocytic phenotypes such as a villus structure and the expression of brush-border enzymes, leads to a reduced expression of ATBF1-A mRNA. We proposed that ATBF1-A regulating APN gene expression in the crypt-villus axis of the small intestine is a landmark of enterocyte differentiation and maturation.
authors.affiliation: First Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Tamaoki
authors.forename: K
authors.initials: K
authors.lastname: Senoo
authors.forename: H
authors.initials: H
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: T
authors.initials: T
authors.lastname: Tada
authors.forename: K
authors.initials: K
authors.lastname: Asai
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000818:Animals; D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology; D018826:CD13 Antigens / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D002087:Butyrates; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C489511:Zfhx3 protein, mouse; C071660:ZFHX3 protein, human; D008156:Luciferases; D018826:CD13 Antigens