DNA Hypomethylation Causes an Increase in DNase-I Sensitivity and an Advance in the Time of Replication of the Entire Inactive X Chromosome
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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.
Characterization of CpG sites that escape methylation on the inactive human X-chromosome.
Moen E, Litwin E, Arnovitz S, Zhang X, Zhang W, Dolan M Epigenetics. 2015; 10(9):810-8.
PMID: 26178744 PMC: 4622068. DOI: 10.1080/15592294.2015.1069461.
Donley N, Thayer M Semin Cancer Biol. 2013; 23(2):80-9.
PMID: 23327985 PMC: 3615080. DOI: 10.1016/j.semcancer.2013.01.001.
DNA methylation profiles of human active and inactive X chromosomes.
Sharp A, Stathaki E, Migliavacca E, Brahmachary M, Montgomery S, Dupre Y Genome Res. 2011; 21(10):1592-600.
PMID: 21862626 PMC: 3202277. DOI: 10.1101/gr.112680.110.
Goren A, Tabib A, Hecht M, Cedar H Genes Dev. 2008; 22(10):1319-24.
PMID: 18443145 PMC: 2377185. DOI: 10.1101/gad.468308.
Surveying CpG methylation at 5'-CCGG in the genomes of rice cultivars.
Ashikawa I Plant Mol Biol. 2001; 45(1):31-9.
PMID: 11247604 DOI: 10.1023/a:1006457321781.