RT Journal Article
SR Electronic
T1 DNA Methylation-Related Chromatin Modification in the Regulation of Mouse δ-Opioid Receptor Gene
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 2032
OP 2039
DO 10.1124/mol.105.011056
VO 67
IS 6
A1 Guilin Wang
A1 Tiancheng Liu
A1 Li-Na Wei
A1 Ping-Yee Law
A1 Horace H. Loh
YR 2005
UL http://molpharm.aspetjournals.org/content/67/6/2032.abstract
AB DNA methylation plays critical roles in gene-silencing through chromatin modification. We reported previously that promoter-region CpG methylation repressed mouse δ-opioid receptor (mDOR) gene expression. In the current study, we demonstrated that the methylation of mDOR gene promoter is correlated with a repressive chromatin structure that has less HaeIII and MspI nuclear accessibility and more deacetylated histone H3 and H4 than that of unmethylated mDOR promoter. Chromatin immunoprecipitation analysis showed the association of a methyl-CpG-binding domain protein 2 (MBD2) with methylated mDOR promoter. Transient expression of MBD2 enhanced the repression of partially methylated mDOR promoter activity, and this repression was partially reversed by treatment of trichostatin A, a specific histone deacetylase inhibitor, indicating that MBD2 may mediate DNA methylation-related chromatin modification through recruiting histone deacetylases to mDOR promoter region. In addition, trichostatin A treatment increased both methylated mDOR promoter activity in a transient transfection assay and endogenous mDOR mRNA level in Neuro2A cells. Taken together, these results demonstrate that the mDOR gene expression is regulated by DNA methylation-related chromatin modification, especially histone acetylation and deacetylation.