Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas.
Cholecystokinin stimulates pancreatic amylase secretion, gallbladder contraction, and pancreatic growth, etc. by binding with high affinity to a cholecystokinin type A receptor (CCKAR). To better understand the expression of CCKAR mRNA in terms of tissue specificity and postnatal development, we determined the methylation status of BssHII sites (5'-B sites) in the rat CCKAR gene promoter. The 5'-B sites in adult pancreas expressing CCKAR mRNA were much less extensively methylated than those in fetal pancreas not expressing the mRNA. In brain, liver, and kidney of adult rats not expressing CCKAR mRNA, the 5'-B sites were methylated. In pancreas, the demethylation level of the sites increased at 21 days after birth. Concomitant with the DNA demethylation level in the 5'-B sites, the mRNA level rose rapidly in 21 days. These results demonstrate that methylation and expression of the CCKAR gene reveal a good inverse correlation.
Matsusue
K
K
Division of Chemotherapy, Division of Gastroenterology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1347, Japan.
Takiguchi
S
S
Takata
Y
Y
Funakoshi
A
A
Miyasaka
K
K
Kono
A
A
D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D010179:Pancreas / Q000254:growth & development*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin