title: Differential methylation of the micro-RNA 7b gene targets postnatal maturation of murine neuronal Mecp2 gene expression.
abstract: DNA methylation and microRNAs (miRNAs) play crucial roles in maturation of postnatal mouse neurons. Aberrant DNA methylation and/or altered miRNA expression cause postnatal neurodevelopmental disorders. In general, DNA methylation in the 5'-flanking region suppresses gene expression through recruitment of methyl-CpG binding domain proteins (MBPs) to the cytosine residues of CpG dinucleotides. X-linked MeCP2 (methyl-CpG binding protein 2), a member of MBPs, is a methylation-associated transcriptional repressor with other functions in the central nervous system (CNS). miRNAs negatively regulate gene expression by targeting the 3'-untranslated region (3'UTR). Some miRNA genes harboring or being embedded in CpG islands undergo methylation-mediated silencing. One such miRNA is miR-7b which is differentially expressed through stages of neurodevelopment. In our present study, we focused on a canonical CpG island located in the 5'-flanking region of the murine miR-7b gene. Hypermethylation of this CpG island down-regulates miR-7b while recruiting MeCP2 to the methylated CpG dinucleotides. Meanwhile, Mecp2, a target of miR-7b, was up-regulated due to lack of restrain exerted by miR-7b during maturation of postnatal (PN) mouse neurons between PN3 and PN14. Our results indicate that miR-7b is a direct downstream gene transcriptional target while also being a negative post-transcriptional regulator of Mecp2 expression. We speculate that this bidirectional feed-back autoregulatory function of miR-7b and Mecp2 while linking DNA methylation and miRNA action maintains the homeostatic control of gene expression necessary during postnatal maturation of mammalian neurons.
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology and Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology and Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Bo-Chul
authors.initials: BC
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology and Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Shanthie
authors.initials: S
authors.lastname: Thamotharan
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology and Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: D020413:3' Untranslated Regions; D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000254:growth & development* / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D018899:CpG Islands; D015870:Gene Expression; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C549243:MIRN7 microRNA, mouse; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs
keywords: DNA methylation; epigenetic regulation; histone deacetylase; miRNA biogenesis; neurodevelopment; transcriptional control
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