| RRC ID |
1853
|
| 著者 |
Yamasaki-Ishizaki Y, Kayashima T, Mapendano CK, Soejima H, Ohta T, Masuzaki H, Kinoshita A, Urano T, Yoshiura K, Matsumoto N, Ishimaru T, Mukai T, Niikawa N, Kishino T.
|
| タイトル |
Role of DNA methylation and histone H3 lysine 27 methylation in tissue-specific imprinting of mouse Grb10.
|
| ジャーナル |
Mol Cell Biol
|
| Abstract |
Mouse Grb10 is a tissue-specific imprinted gene with promoter-specific expression. In most tissues, Grb10 is expressed exclusively from the major-type promoter of the maternal allele, whereas in the brain, it is expressed predominantly from the brain type promoter of the paternal allele. Such reciprocally imprinted expression in the brain and other tissues is thought to be regulated by DNA methylation and the Polycomb group (PcG) protein Eed. To investigate how DNA methylation and chromatin remodeling by PcG proteins coordinate tissue-specific imprinting of Grb10, we analyzed epigenetic modifications associated with Grb10 expression in cultured brain cells. Reverse transcriptase PCR analysis revealed that the imprinted paternal expression of Grb10 in the brain implied neuron-specific and developmental stage-specific expression from the paternal brain type promoter, whereas in glial cells and fibroblasts, Grb10 was reciprocally expressed from the maternal major-type promoter. The cell-specific imprinted expression was not directly related to allele-specific DNA methylation in the promoters because the major-type promoter remained biallelically hypomethylated regardless of its activity, whereas gametic DNA methylation in the brain type promoter was maintained during differentiation. Histone modification analysis showed that allelic methylation of histone H3 lysine 4 and H3 lysine 9 were associated with gametic DNA methylation in the brain type promoter, whereas that of H3 lysine 27 regulated by the Eed PcG complex was detected in the paternal major-type promoter, corresponding to its allele-specific silencing. Here, we propose a molecular model that gametic DNA methylation and chromatin remodeling by PcG proteins during cell differentiation cause tissue-specific imprinting in embryonic tissues.
|
| 巻・号 |
27(2)
|
| ページ |
732-42
|
| 公開日 |
2007-1-1
|
| DOI |
10.1128/MCB.01329-06
|
| PII |
MCB.01329-06
|
| PMID |
17101788
|
| PMC |
PMC1800802
|
| MeSH |
Animals
Brain / cytology
Cell Differentiation
Cells, Cultured
Chromatin Assembly and Disassembly
Crosses, Genetic
DNA Methylation*
Epigenesis, Genetic*
GRB10 Adaptor Protein / genetics
GRB10 Adaptor Protein / metabolism*
Genomic Imprinting*
Histones / metabolism*
Lysine / metabolism*
Methylation
Mice
Neuroglia / cytology
Neurons / cytology
Polycomb-Group Proteins
Promoter Regions, Genetic
Repressor Proteins / genetics
Repressor Proteins / metabolism
|
| IF |
3.611
|
| 引用数 |
38
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00213 |
