Activation of collagen IV gene expression in F9 teratocarcinoma cells by 3-deazaadenosine analogs. Indirect inhibitors of methylation.
3-Deazaadenosine analogs can function as inhibitors and also as alternative substrates of S-adenosylhomocysteine (AdoHcy) hydrolase. In cells treated with the analogs, AdoHcy invariably accumulates, leading to inhibition of cellular methylation. F9 teratocarcinoma cells, stably transfected with two collagen (IV) promoter-enhancer-CAT constructs and treated with 10 microM 3-deazaadenosine, 3-deaza-(+-)-aristeromycin or 3-deazaneplanocin, showed a strong induction of CAT activities without affecting differentiation. In comparison, the same 3-deaza analogs did not affect the CAT activity in F9 cells transfected with the beta-actin promoter-CAT construct. Furthermore, Northern blot analysis of endogenous mRNA from wild-type F9 cells treated with the 3-deaza nucleosides all showed an induction of the collagen alpha 1(IV) chain mRNA. Thus, the 3-deaza analogs most likely affect DNA methylation because their results are consistent with the previous observation that the integrated collagen alpha 1(IV) promoter-enhancer constructs were activated with 5-azacytidine.
Chiang
P K
PK
Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Burbelo
P D
PD
Brugh
S A
SA
Gordon
R K
RK
Fukuda
K
K
Yamada
Y
Y
D043383:Adenosylhomocysteinase; D015152:Blotting, Northern; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007536:Isomerism; D008745:Methylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013379:Substrate Specificity; D013724:Teratoma / Q000378:metabolism*; D014162:Transfection; D014372:Tubercidin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; C018258:3-deazaadenosine; D003094:Collagen; D015500:Chloramphenicol O-Acetyltransferase; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D014372:Tubercidin