Abstract
The steady state level of DNA methyltransferase mRNA is markedly increased as growth-arrested Balb/c 3T3 cells progress into the S phase of the cell cycle. mRNA abundance is reduced to the basal level before termination of DNA synthesis activity. Maintenance DNA methylation activity in nuclear extracts follows a similar pattern with two exceptions. (a) A small peak of DNA methylation activity is detected in early G1 phase. (b) The extinction of DNA methylation activity lags behind the termination of DNA synthesis. Nuclear runon experiments demonstrate that the gene is transcribed in growth-arrested cells, and expression of the gene is post-transcriptionally regulated. We suggest that this mode of regulation of the DNA methyltransferase gene might play an important role in determining and maintaining DNA methylation patterns.
Highlights
From the Department of Pharmacology and Therapeutics, patterns in vertebrate cells
We test the hypothesis that mRNA is markedly increasedas growth-arrested Balb/ regulation of DNA methyltransferase gene expression is asc 3T3 cells progress into theS phase of thecell cycle. sociated with the proliferative state of the cell and determine mRNA abundance is reduced to the basal level before termination of DNA synthesis activity
Nuclear mesenchymal line, isolated by Todaro and Green ( l l ), which runon experiments demonstrate that the geneis tran- can be maintained in a state in which they exhibit stringent scribed in growth-arrestecdells, and expression of the gene is post-transcriptionallyregulated. We suggest that this mode of regulation of theDNA methyltransferase gene might playan important role in determining and maintainingDNA methylation patterns
Summary
Entia affinities of the DNA methyltranferaseprotein for different sites might play an important role in determining the final methylation pattern [1, 5]. McGill University, Montreal, Quebec H3G 1Y6, Canada ferase activity plays such a role, it should be regulated with and the lIDepartment of Genetics, Harvard Medical School, respect to DNA synthesis activity. We test the hypothesis that mRNA is markedly increasedas growth-arrested Balb/ regulation of DNA methyltransferase gene expression is asc 3T3 cells progress into theS phase of thecell cycle. Sociated with the proliferative state of the cell and determine mRNA abundance is reduced to the basal level before termination of DNA synthesis activity. Maintenance DNA methylation activity in nuclear extracts follows the level at which it is regulated using the mouse fibroblast Balb/c 3T3 cell as a growth-induced cell system. A similar patternwith two exceptions. (a)A small peak of DNA methylation activity is detected in early GI
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