DNA hypomethylation causes an increase in DNase-I sensitivity and an advance in the time of replication of the entire inactive X chromosome.
We have examined the effect of 5-azacytidine (5-aza-C) induced hypomethylation of DNA on the time of replication and DNase I sensitivity of the X chromosomes of female Gerbillus gerbillus (rodent) lung fibroblast cells. Using in situ nick translation to visualise the potential state of activity of large regions of metaphase chromosomes we show that 5-aza-C causes a dramatic increase in the DNase-I sensitivity of the entire inactive X chromosome of female G. gerbillus cells and this increase in nuclease sensitivity correlates with a large shift in the time of replication of the inactive X chromosome from late S phase to early S phase. These effects of 5-aza-C on the inactive X chromosome are associated with a 15% decrease in DNA methylation. Our results indicate that DNA methylation concomitantly affects both the time of replication and the chromatin conformation of the inactive X chromosome.
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004261:DNA Replication; D003850:Deoxyribonuclease I / Q000378:metabolism*; D005260:Female; D005849:Gerbillinae; D007621:Karyotyping; D007700:Kinetics; D008168:Lung / Q000166:cytology*; D008745:Methylation; D014960:X Chromosome
D004247:DNA; D003850:Deoxyribonuclease I