| RRC ID |
26
|
| 著者 |
Yamasaki Y, Kayashima T, Soejima H, Kinoshita A, Yoshiura K, Matsumoto N, Ohta T, Urano T, Masuzaki H, Ishimaru T, Mukai T, Niikawa N, Kishino T.
|
| タイトル |
Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air.
|
| ジャーナル |
Hum Mol Genet
|
| Abstract |
The mouse insulin-like growth factor II receptor (Igf2r) gene and its antisense transcript Air are reciprocally imprinted in most tissues, but in the brain, Igf2r is biallelically expressed despite the imprinted Air expression. To investigate the molecular mechanisms of such brain-specific relaxation of Igf2r imprinting, we analyzed its expression and epigenetic modifications in neurons, glial cells and fibroblasts by the use of primary cortical cell cultures. In glial cells and fibroblasts, Igf2r was maternally expressed and Air was paternally expressed, whereas in the primary cultured neurons, Igf2r was biallelically expressed and Air was not expressed. In the differentially methylated region 2 (DMR2), which includes the Air promoter, allele-specific DNA methylation, differential H3 and H4 acetylation and H3K4 and K9 di-methylation were maintained in each cultured cell type. In DMR1, which includes the Igf2r promoter, maternal-allele-specific DNA hypomethylation, histones H3 and H4 acetylation and H3K4 di-methylation were apparent in glial cells and fibroblasts. However, in neurons, biallelic DNA hypomethylation and biallelic histones H3 and H4 acetylation and H3K4 di-methylation were detected. These data indicate that lack of reciprocal imprinting of Igf2r and Air in the brain results from neuron-specific relaxation of Igf2r imprinting associated with neuron-specific histone modifications in DMR1 and lack of Air expression. Our observation of biallelic Igf2r expression with no Air expression in neurons sheds light on the function of Air as a critical effector in Igf2r silencing and suggests that neuron-specific epigenetic modifications related to the lineage determination of neural stem cells play a critical role in controlling imprinting by antisense transcripts.
|
| 巻・号 |
14(17)
|
| ページ |
2511-20
|
| 公開日 |
2005-9-1
|
| DOI |
10.1093/hmg/ddi255
|
| PII |
ddi255
|
| PMID |
16037066
|
| MeSH |
Animals
Brain / embryology
DNA Methylation
Embryonic Development
Gene Expression Regulation, Developmental
Genomic Imprinting
Histones / genetics
Histones / metabolism*
Mice
Neurons / physiology*
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Receptor, IGF Type 2 / genetics*
|
| IF |
5.101
|
| 引用数 |
55
|
|
WOS 分野
|
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00213 |
