DNA METHYLATION CONTRIBUTES TO EXPRESSION OF THE HUMAN NEUROTENSIN NEUROMEDIN N GENE/

Citation
Zz. Dong et al., DNA METHYLATION CONTRIBUTES TO EXPRESSION OF THE HUMAN NEUROTENSIN NEUROMEDIN N GENE/, American journal of physiology: Gastrointestinal and liver physiology, 37(3), 1998, pp. 535-543
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
ISSN journal
0193-1857
Volume
37
Issue
3
Year of publication
1998
Pages
535 - 543
Database
ISI
SICI code
0193-1857(1998)37:3<535:DMCTEO>2.0.ZU;2-I
Abstract
The gut and Liver share a common embryological origin. The gene encodi ng the gut hormone neurotensin/neuromedin N (NT/N) is expressed in the adult small bowel, and NT/N is transiently expressed in the fetal liv er, suppressed in the adult liver, and reexpressed in certain liver ca ncers. In our present study, we found that the NT/N gene was expressed at high levels in the human hepatoma cell line Hep 3B but was not exp ressed in Hep G2 cells. To further determine the mechanisms regulating NT/N expression, we performed Southern blotting and gene cloning tech niques. Neither alteration nor mutation of the NT/N gene was responsib le for this differential NT/N expression pattern. Human NT/N promoter constructs were transfected into either Hep 3B or Hep G2. Both cell li nes supported NT/N transcription, indicating that the absence of NT/N expression in Hep G2 cells was due to mechanisms other than the absenc e of positive transcription factors. The role of DNA methylation was n ext assessed. Methylation of NT/N promoter constructs in vitro resulte d in a 67-fold reduction in promoter activity, whereas treatment with the demethylating agent 5-azacytidine induced NT/N expression in Hep G 2 cells, thus suggesting that DNA methylation plays a role in the expr ession of the gut endocrine gene NT/N. Defining the mechanisms regulat ing NT/N expression in these hepatic-derived cell lines will provide n ot only a better understanding of cell-specific and developmental regu lation of a gut endocrine gene but also possible insight into liver ce ll lineage patterns and the derivation of certain hepatocellular cance rs.