Characterization of promoter elements regulating the expression of the human neurotensin/neuromedin N gene

Xiaofu Wang, Pat Gulhati, Jing Li, Paul R. Dobner, Heidi Weiss, Courtney Townsend, B. Mark Evers

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Expression of the gene encoding neurotensin/neuromedin N (NT/N) is mostly limited to the brain and specialized enteroendocrine N cells in the distal small intestine. We have identified key regulatory elements in the promoter region that are involved in human NT/N (hNT/N) gene expression in the novel human endocrine cell line, BON, which resembles intestinal N cells in several important aspects including NT/N precursor protein processing, ratios of different NT/N mRNA isoforms, and high levels of constitutive expression of the NT/N gene. In this study, we demonstrated multiple cis-regulatory elements including a proximal region containing a cAMP-responsive element (CRE)/AP-1-like element that binds both the AP-1 and CRE-binding protein (CREB)/ATF proteins (c-Jun, ATF-1, ATF-2, JunD, and CREB). Similar to the rat NT/N gene, this region is critical for constitutive hNT/N gene expression. Moreover, we identified a novel region that binds the orphan hormone receptor, NR2F2. We have demonstrated that the C terminus of NR2F2 strongly represses hNT/N transcription, whereas an N-terminal domain antagonizes this repressive effect. Regulation of NT/N expression by NR2F2 may have important consequences for lipid metabolism. We speculate that a complex interplay between the proximal CRE/AP-1-like motif and NR2F2 binding region exists to regulate hNT/N expression, which is critical for the high level of constitutive expression of NT/N in enteroendocrine cells. Finally, the BON cell line provides a unique model to characterize the factors regulating expression of the hNT/N gene and to better understand the mechanisms responsible for terminal differentiation of the N cell lineage in the gut.

Original languageEnglish (US)
Pages (from-to)542-554
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number1
DOIs
StatePublished - Jan 7 2011

Fingerprint

neuromedin N
Neurotensin
Genes
Transcription Factor AP-1
Enteroendocrine Cells
Gene Expression
Gene expression
Carrier Proteins
Cells
Proto-Oncogene Proteins c-jun
RNA Isoforms
Cell Line
Orphaned Children
Gene encoding
Endocrine Cells
Cell Lineage
Transcription
Lipid Metabolism
Genetic Promoter Regions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Characterization of promoter elements regulating the expression of the human neurotensin/neuromedin N gene. / Wang, Xiaofu; Gulhati, Pat; Li, Jing; Dobner, Paul R.; Weiss, Heidi; Townsend, Courtney; Evers, B. Mark.

In: Journal of Biological Chemistry, Vol. 286, No. 1, 07.01.2011, p. 542-554.

Research output: Contribution to journalArticle

Wang, Xiaofu ; Gulhati, Pat ; Li, Jing ; Dobner, Paul R. ; Weiss, Heidi ; Townsend, Courtney ; Evers, B. Mark. / Characterization of promoter elements regulating the expression of the human neurotensin/neuromedin N gene. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 1. pp. 542-554.
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