Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes
- 635 Downloads
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.
KeywordsMeCP2 Myelination Rett syndrome Oligodendrocytes MBP PLP MOG MOBP BDNF YY1
This work was supported by grants from the Department of Biotechnology (DBT), New Delhi, India, (sanction order no. BT/PR4974/MED/30/773/2012 dated 10/09/2013). We thank the Department of Biotechnology (DBT), New Delhi, India, and University Grants Commission (UGC), New Delhi, India (UGC reference no. and date- F. no. 41-148/2012 (SR) dated 13/07/2012) for awarding Junior Research Fellows (JRFs) to Kedarlal Sharma and Juhi Singh, respectively. We are also very much thankful to DBT-ILSPARE Programme, for providing us the Confocal microscopy and Real-Time PCR facility in Dr. Vikram Sarabhai Science Block, Faculty of Science, MSU, Baroda.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S (2009) Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus. Int J Neuropsychopharmacol 12(1):73–82CrossRefPubMedGoogle Scholar
- Fulton D, Paez PM, Campagnoni AT (2009) The multiple roles of myelin protein genes during the development of the oligodendrocyte. ASN Neuro 2(1), AN20090051Google Scholar
- Jung BP, Jugloff DGM, Zhang G, Logan R, Brown S, Eubanks JH (2003) The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells ABSTRACT. J Neurobiol 55(1):86–96Google Scholar
- Khorshid Ahmad, T., Acosta, C., Cortes, C., Lakowski, T. M., Gangadaran, S., & Namaka, M. (2015). Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS). Molecular neurobiology, 1-16Google Scholar
- Kishi N, Macklis J (2004) MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci 27(3):306–321Google Scholar
- Quarles, R. H., Macklin, W. B., & Morell, P. (2006). Biochemistry, 51–72Google Scholar
- Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY (2002) Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 11(2):115–124Google Scholar