Evidence for gene silencing by endogenous DNA methylation

被引：34

作者：

Holliday, R ^{[1
]}

Ho, T ^{[1
]}

机构：

[1] CSIRO, Sydney Lab, N Ryde, NSW 2113, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1998年 / 95卷 / 15期

关键词：

D O I：

10.1073/pnas.95.15.8727

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Transformed cells can spontaneously silence genes by de novo methylation, and it is generally assumed that this is due to DNA methyltransferase activity. We have tested the alternative hypothesis that gene silencing could be due to the uptake of 5-methyl-dCMP into DNA, via the di- and triphosphonucleotides. 5-Methyl-dCMP would be present in cells from the ongoing repair of DNA, We have isolated a strain of Chinese hamster ovary (CHO) cells, designated HAM(-), which spontaneously silences two tested genes at a very high frequency, We have shown that this strain incorporates 5-[H-3]methyldeoxycytidine into 5-methylcytosine and thymine in DNA, It also has low 5-methyl-dCMP deaminase activity. Another HAM(+) strain has high deaminase activity and a very low frequency of gene silencing. The starting strain, CHO K1, has a phenotype intermediate between HAM(-) and HAM(+).

引用

页码：8727 / 8732

页数：6