Antithetic effects of MBD2a on gene regulation.
DNA methylation is essential for epigenetic gene regulation during development. The cyclic AMP (cAMP)-responsive element (CRE) is found in the promoter of many cAMP-regulated genes and plays important roles in their gene expression. Methylation occurs on the CRE site and results in transcriptional repression via a direct mechanism, that is, prevention by the methyl group of binding of the cAMP-responsive factor CREB to this site. A recent study indicated that the nucleosome is also important in repressing transcription. In this study, we investigated the regulation of transcriptional repression on methylated CRE. We focused on methyl-CpG binding domain protein 2 (MBD2). MBD2 consists of two forms, MBD2a and MBD2b, the latter lacking the N-terminal extension of MBD2a. Unexpectedly, we found that MBD2a, but not MBD2b, promoted activation of the unmethylated cAMP-responsive genes. An in vivo binding assay revealed that MBD2a selectively interacted with RNA helicase A (RHA), a component of CREB transcriptional coactivator complexes. MBD2a and RHA cooperatively enhanced CREB-dependent gene expression. Interestingly, coimmunoprecipitation assays demonstrated that MBD2a binding to RHA was not associated with histone deacetylase 1. Our results indicate a novel role for MBD2a in gene regulation.
Fujita
Hidetoshi
H
Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa 216-8512, Japan.
Fujii
Ryouji
R
Aratani
Satoko
S
Amano
Tetsuya
T
Fukamizu
Akiyoshi
A
Nakajima
Toshihiro
T
D001324:Autoantigens / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins; D020365:RNA Helicases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D001324:Autoantigens; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C115368:MBD2 protein; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D004247:DNA; D000242:Cyclic AMP; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases