TY - JOUR
T1 - Differential promoter methylation and histone modification contribute to the brain specific expression of the mouse Mbu-1 gene
AU - Kim, Byungtak
AU - Kang, Seongeun
AU - Kim, Sun Jung
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - 5-aza-2'-deoxycytidine
KW - Chromatin immunoprecipitation
KW - Histone modification
KW - Mouse brain unigene
KW - Promoter methylation
UR - http://www.scopus.com/inward/record.url?scp=84870362529&partnerID=8YFLogxK
U2 - 10.1007/s10059-012-0182-3
DO - 10.1007/s10059-012-0182-3
M3 - Article
C2 - 23076708
AN - SCOPUS:84870362529
SN - 1016-8478
VL - 34
SP - 433
EP - 437
JO - Molecules and Cells
JF - Molecules and Cells
IS - 5
ER -