title: Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes.
abstract: Methyl CpG binding protein 2 (MeCP2) is a multifunctional protein which binds to methylated CpG, mutation of which cause a neurodevelopmental disorder, Rett syndrome. MeCP2 can function as both transcriptional activator and repressor of target gene. MeCP2 regulate gene expression in both neuron and glial cells in central nervous system (CNS). Oligodendrocytes, the myelinating cells of CNS, are required for normal functioning of neurons and are regulated by several transcription factors during their differentiation. In current study, we focused on the role of MeCP2 as transcription regulator of myelin genes in cultured rat oligodendrocytes. We have observed expression of MeCP2 at all stages of oligodendrocyte development. MeCP2 knockdown in cultured oligodendrocytes by small interference RNA (siRNA) has shown increase in myelin genes (myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated oligodendrocyte basic protein (MOBP)), neurotrophin (brain-derived neurotrophic factor (BDNF)), and transcriptional regulator (YY1) transcripts level, which are involved in regulation of oligodendrocyte differentiation and myelination. Further, we also found that protein levels of MBP, PLP, DM-20, and BDNF also significantly upregulated in MeCP2 knockdown oligodendrocytes. Our study suggests that the MeCP2 acts as a negative regulator of myelin protein expression.
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India.
authors.forename: Kedarlal
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India.
authors.forename: Juhi
authors.initials: J
authors.lastname: Singh
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India. pillaippp@gmail.com.
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Pillai
authors.affiliation: , Winnipeg, Manitoba, Canada.
authors.forename: Emma E
authors.initials: EE
authors.lastname: Frost
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; C489071:Plp1 protein, rat; D012333:RNA, Messenger; D050986:YY1 Transcription Factor; C494700:Yy1 protein, rat
keywords: BDNF; MBP; MOBP; MOG; MeCP2; Myelination; Oligodendrocytes; PLP; Rett syndrome; YY1