AT motif binding factor 1-A (ATBF1-A) negatively regulates transcription of the aminopeptidase N gene in the crypt-villus axis of small intestine.
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.
Kataoka
H
H
First Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Japan.
Joh
T
T
Miura
Y
Y
Tamaoki
T
T
Senoo
K
K
Ohara
H
H
Nomura
T
T
Tada
T
T
Asai
K
K
Kato
T
T
Itoh
M
M
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
D002087:Butyrates; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C489511:Zfhx3 protein, mouse; C071660:ZFHX3 protein, human; D008156:Luciferases; D018826:CD13 Antigens