5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation

Citation
Jp. Jost et al., 5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation, NUCL ACID R, 29(21), 2001, pp. 4452-4461
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEIC ACIDS RESEARCH
ISSN journal
0305-1048 → ACNP
Volume
29
Issue
21
Year of publication
2001
Pages
4452 - 4461
Database
ISI
SICI code
0305-1048(20011101)29:21<4452:5DGPIT>2.0.ZU;2-7
Abstract
Changes in gene expression during mouse myoblast differentiation were monit ored by DNA microarray hybridisation. Four days after the onset of differen tiation 2.37% of the genes increased in activity from a value of zero, wher eas during the same time 1.68% of total genes had decreased expression. Dur ing the first 24 h of differentiation an average of 700 000 CpG sites per h aploid genome were demethylated. Maximal loss of DNA methylation is attaine d after 2 days of differentiation, followed by a gradual remethylation. The highest demethylation is observed in highly repeated DNA sequences, follow ed by single copy sequences. When DNA replication is inhibited by aphidicol in or l-mimosine this genome-wide demethylation is still observed. During t he first 3 h of differentiation there is an increase in the number of hemim ethylated CpG sites, which disappear rapidly during the course of genome-wi de hypomethylation. Transfection of cells with an antisense morpholino olig onucleotide to 5-methylcytosine DNA glycosylase (G/T mismatch DNA glycosyla se) decreases both the activity of the enzyme and genome-wide demethylation . It is concluded that the genome-wide loss of DNA methylation in different iating mouse myoblasts occurs in part by formation of hemimethylated CpG si tes, which can serve as the substrate for 5-methylcytosine-DNA glycosylase.