Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene.

Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Research Abstract Details 

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Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Abstract Text:

M D S Jamaluddin,Irene Chen,Fan Yang,Xiaohua Jiang,Michael Jan,Xiaoming Liu,Andrew I Schafer,William Durante,Xiaofeng Yang,Hong Wang,M D S Jamaluddin,Irene Chen,Fan Yang,Xiaohua Jiang,Michael Jan,Xiaoming Liu,Andrew I Schafer,William Durante,Xiaofeng Yang,Hong Wang,

We reported previously that homocysteine (Hcy) inhibits endothelial cell (EC) growth by transcriptional inhibition of the cyclin A gene via a hypomethylation-related mechanism. In this study, we examined the effect of Hcy on epigenetic modification of the cyclin A gene and its biologic role in human ECs. Cyclin A mRNA levels were significantly suppressed by Hcy and a DNA methyltransferase inhibitor. The cyclin A promoter contains a CpG island spanning a 477-bp region (-277/200). Bisulfite sequencing followed by polymerase chain reaction (PCR) amplification of the cyclin A promoter (-267/37) showed that Hcy eliminated methylation at 2 CpG sites in the cyclin A promoter, one of which is located on the cycle-dependent element (CDE). Mutation of CG sequence on the CDE leads to a 6-fold increase in promoter activity. Hcy inhibited DNA methyltransferase 1 (DNMT1) activity by 30%, and reduced the binding of methyl CpG binding protein 2 (MeCP2) and increased the bindings of acetylated histone H3 and H4 in the cyclin A promoter. Finally, adenovirus-transduced DNMT1 gene expression reversed the inhibitory effect of Hcy on cyclin A expression and EC growth inhibition. In conclusion, Hcy inhibits cyclin A transcription and cell growth by inhibiting DNA methylation through suppression of DNMT1 in ECs.

Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Publishing Authors By Initials

MD Jamaluddin,I Chen,F Yang,X Jiang,M Jan,X Liu,AI Schafer,W Durante,X Yang,H Wang,MD Jamaluddin,I Chen,F Yang,X Jiang,M Jan,X Liu,AI Schafer,W Durante,X Yang,H Wang,

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Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Blood

VOLUME: 110

Page Numbers: 3648-55

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 13

MONTH: 08

YEAR: 2007

Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

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Grant and Affiliation Information for Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene.

AFFILIATION: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL82774

ACRONYM: HL

MEDLINETA: Blood

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