5-Aza-2'-deoxycytidine induces histone hyperacetylation of mouse centromeric heterochromatin by a mechanism independent of DNA demethylation.
5-Aza-2'-deoxycytidine (5-azadC) is widely used as a potent inhibitor of DNA methyltransferase. Cells treated with this drug show various phenomena such as the reactivation of repressed genes, change in replication timing, and decondensation of heterochromatin. A number of studies using this drug have been reported so far but it is still controversial whether such changes are due to 5-azadC-induced demethylation itself or the side effects of the drug. Here we report that 5-azadC treatment induces histone hyperacetylation in mouse centromeric heterochromatin which normally contains methylated DNA and hypoacetylated histones. Treatment also affects the intranuclear distribution of histone deacetylase 2 (HDAC2). However, histone hyperacetylation was not observed in DNA methyltransferase 1-deficient cells with a reduced level of genomic DNA methylation. Our results suggest that 5-azadC-induced histone hyperacetylation is independent of DNA demethylation and that DNA methylation is not essential for the maintenance of the histone hypoacetylated state in centromeric heterochromatin.
Takebayashi
S
S
Faculty of Bioresources, Mie University, 1515 Kamihama, Tsu, Mie, 514-8507, Japan. ol31233@cc.mie-u.ac.jp
Nakao
M
M
Fujita
N
N
Sado
T
T
Tanaka
M
M
Taguchi
H
H
Okumura
K
K
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D002503:Centromere / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D006570:Heterochromatin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D012097:Repressor Proteins; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D001374:Azacitidine