Differential promoter methylation and histone modification contribute to the brain specific expression of the mouse Mbu-1 gene.
Mbu-1 (Csrnp-3) is a mouse gene that was identified in our previous study as showing highly restricted expression to the central nervous system. In this study, to elucidate the regulatory mechanism for tissue specificity of the gene, epigenetic approaches that identify the profiles of CpG methylation, as well as histone modifications at the promoter region were conducted. Methylation-specific PCR revealed that the CpG sites in brain tissues from embryo to adult stages showed virtually no methylation (0.052-0.67%). Lung (9.0%) and pancreas (3.0%) also showed lower levels. Other tissues such as liver, kidney, and heart showed much higher methylation levels ranging from approximately 39-93%. Treatment of 5-aza-2'-deoxycytidine (5-Aza-dC) significantly decreased promoter methylation, reactivating Mbu-1 expression in NG108-15 and Neuro-2a neuronal cells. Chromatin immunoprecipitation assay revealed that 5-Aza-dC decreased levels of acetylated H3K9 and methylated H3K4, and increased methylated H3K9. This result indicates that CpG methylation converses with histone modifications in an opposing sense of regulating Mbu-1 expression.
Department of Life Science, Dongguk University-Seoul, Seoul 100-715, Korea.
Byungtak
B
Kim
Seongeun
S
Kang
Sun Jung
SJ
Kim
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D000077209:Decitabine; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C528237:Taip2 protein, mouse; D000077209:Decitabine; D001374:Azacitidine