A silencer inhibitor confers specific expression of intestinal trefoil factor in gobletlike cell lines

D. Iwakiri, D. K. Podolsky

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Intestinal trefoil factor (ITF) is selectively expressed in intestinal goblet cells. Previous studies identified cis-regulatory elements in the proximal promoter of ITF, but these were insufficient to recapitulate the exquisite tissue- and cell-specific expression of native ITF in vivo. Preliminary studies suggested that goblet cell-specific expression of murine ITF requires elements far upstream that include a silencer element that effectively prevents ITF expression in non-goblet cells. Transient transfection studies using native or mutant ITF 5′-flanking sequences identified a region that restores expression in goblet cells. This element, designated goblet cell silencer inhibitor (GCSI) element, enables human and murine goblet cell-like cell lines to override the silencing effect of more proximal elements. The GCSI has no intrinsic enhancer activity and regulates expression only when the silencer element is present. Ligation of GCSI and silencer elements to sucrase-isomaltase conferred goblet cell-specific expression. Goblet cells but not non-goblet cells possess a nuclear protein that binds to the GCSI regulatory element (GCSI binding protein; GCSI-BP). Both transient transfection and gel mobility shift assay studies localize the GCSI and GCSI-BP to -2216 to -2204. We conclude that goblet cell-specific transcription of ITF in vivo depends on a regulatory element designated GCSI.

Original languageEnglish (US)
Pages (from-to)G1114-G1123
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume280
Issue number6 43-6
DOIs
StatePublished - 2001

Keywords

  • Antisilencing
  • Intestinal goblet cells
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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