Role of DNA methylation in stable gene repression.
A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-)(/)(-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to additional repression mechanisms that also impact on histone acetylation, and the data suggest that late replication timing may play an important role in this process.
Lande-Diner
Laura
L
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Ein Kerem, 91120 Jerusalem, Israel.
Zhang
Jianmin
J
Ben-Porath
Ittai
I
Amariglio
Ninette
N
Keshet
Ilana
I
Hecht
Merav
M
Azuara
Veronique
V
Fisher
Amanda G
AG
Rechavi
Gideon
G
Cedar
Howard
H
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000737:chemistry; D018899:CpG Islands; D004247:DNA / Q000737:chemistry; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000502:physiology*; D019175:DNA Methylation; D004261:DNA Replication; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis
D002843:Chromatin; D006657:Histones; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse