Inducible expression of microRNA-194 is regulated by HNF-1α during intestinal epithelial cell differentiation

Kimihiro Hino, Kiichiro Tsuchiya, Taro Fukao, Kotaro Kiga, Ryuichi Okamoto, Takanori Kanai, Mamoru Watanabe

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Maintenance of the intestinal epithelium is based on well-balanced molecular mechanisms that confer the stable and continuous supply of specialized epithelial cell lineages from multipotent progenitors. Lineage commitment decisions in the intestinal epithelium system involve multiple regulatory systems that interplay with each other to establish the cellular identities. Here, we demonstrate that the microRNA system could be involved in intestinal epithelial cell differentiation, and that microRNA-194 (miR-194) is highly induced during this process. To investigate this inducible expression mechanism, we identified the genomic structure of the miR-194-2, -192 gene, one of the inducible class of miR-194 parental genes. Furthermore, we identified its transcriptional regulatory region that contains a consensus-binding motif for hepatocyte nuclear factor-1α (HNF-1α), which is well known as a transcription factor to regulate gene expression in intestinal epithelial cells. By chromatin immunoprecipitation assay and luciferase reporter analysis, we revealed that pri-miR-194-2 expression is controlled by HNF-1α, and its consensus binding region is required for the transcription of pri-miR-194-2 in vivo in an intestinal epithelial cell line, Caco-2. Our observations indicate that microRNA genes could be targets of lineage-specific transcription factors and that microRNAs are regulated by a tissue-specific manner in the intestinal epithelium. Therefore, our work suggests that induced expression of these microRNAs have important roles in intestinal epithelium maturation. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish
Pages (from-to)1433-1442
Number of pages10
JournalRNA
Volume14
Issue number7
DOIs
Publication statusPublished - 2008 Jul

Keywords

  • Caco-2
  • Differentiation
  • HNF-1α
  • Intestine
  • miR-194
  • microRNA

ASJC Scopus subject areas

  • Molecular Biology

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