Mecp2 is in many mammals an important regulator of neuronal function and development. It affects all cell types, especially neurons but also astrocytes, oligodendrocytes, and glial cells. Mecp2 plays an important role in neuronal differentiation, maturation, morphology and function and influences synaptic plasticity. Mutations impairing the proper function of Mecp2 are mainly associated with the Rett syndrome but may also contribute to other neurological disorders like schizophrenia, FASD (fetal alcohol syndrome), PPM-X-syndrome, autism, Prader-Will-syndrome, and Angelman-syndrome. Dependant on the cofactors Mecp2 acts as an activator or repressor of transcription and micro RNA production. It affects RNA splicing and regulates chromatin structure together with HP1 and interferes in methylation of DNA (epigenetics). The expression of Mecp2 itself is highly regulated by promotor elements, cis-regulatory elements, polyadenylation, promotor DNA methylation and miRNA.
Please cite this pathways as: http://www.wikipathways.org/instance/WP3584
Ehrhart et al. 2016 http://dx.doi.org/10.1186/s13023-016-0545-5 c74nuclear receptor co-repressor 1c4fc74myelin transcription factor 1proof of Mecp2 inhibition in Oligodendrocytesd06POU domain, class 4, transcription factor 1 d06The effect of Mecp2 on miR-184 is discussed controversially: Nomura et al. 2008 reports an Mecp2 dependant repression of miR-184 while Liu et al. 2010 reports no effect of Mecp2 but an MBD1 dependant regulation of miR-184d7ba0df4fc74apolipoprotein C-IIc74a0dinfluences neuronal stem cell proliferation and differentiationbcff4fbrain derived neurotrophic factorc74neurofibromatosis 1a12Somatostatincd2chromatin factor, data obtained using human cell line and mouse primary tissued46neuronal regeneration related proteinfucosyltransferase 8c74c74methyl CpG binding protein 2POU domain, class 3, transcription factor 2c74fibroblast growth factor 3c74Base sequence! It is unclear which mature miRNA was tested.f4ftructural maintenance of chromosomes 3beereported for human onlybinding site at 3'UTR of Mecp2 reported, regulative effect unclearbfarelated to FASD (fetal alcohole spectrum disorder)NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1e24f4finhibition of Mecp2 expression only reported for human!c20myocyte enhancer factor 2Ccd2transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) c74N-Methyl-D-aspartic acidataxin 2 binding protein 1, Rbfox1cd22',3'-cyclic nucleotide 3' phosphodiesterasebf3d5ed35d4cbd9histone H3 lysine 27 methyltransferasebcfguanidinoacetate methyltransferasecd2c74f4fHistone 3bcfopioid receptor, kappa 1cd2f4fRho guanine nucleotide exchange factor (GEF) 26bd9c74bd9trans-acting transcription factor 1ecfa0db72TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factorecfHNRNPH1e66f4fcysteine and glycine-rich protein 1f4fdistal-less homeobox 5controls GABA productione24a0df4freported for human umbilical vein endothelial cells onlyc56f4fcell adhesion molecule-related/down-regulated by oncogenesMyelin transcription factor 1d06CCAAT/enhancer binding protein (Cebpd), deltac74f4fmyelin basic proteinbe3c74B cell leukemia/lymphoma 6d06gamma-aminobutyric acid (GABA) C receptor, subunit rho 2bd9CCCTC-binding factor ecftrans-acting transcription factor 3c74no connection between Mecp2 and miR-187 in other sources than [3]c74beePRP3 pre-mRNA processing factor 3 homolog (yeast)f56E2F transcription factor 1 c74Glutamate receptord9ec74RE1-silencing transcription factorSilences Mecp2 in non-neuronal tissued06myelin-associated glycoproteinbe3fibroblast growth factor 2c74G protein-regulated inducer of neurite outgrowth 1cd2tet methylcytosine dioxygenase 1b51f4fHnrnpfheterogeneous nuclear ribonucleoprotein Fe66f4fdata obtained with human cell line and mouse primary tissueY box protein 1d46e24methyl CpG binding protein 2methyl CpG binding protein 2methyl CpG binding protein 2trans-acting transcription factor 1ecfd06d5ebrain derived neurotrophic factorc74guanidinoacetate methyltransferasecd2d5emethyl CpG binding protein 223351786PubMedMeCP2 modulates gene expression pathways in astrocytesMol Autism2013Dag H YasuiHuichun XuKeith W DunawayJanine M LaSalleLee-Way JinIzumi Maezawa21423409PubMedSynaptic signaling and aberrant RNA splicing in autism spectrum disorders.Front Synaptic Neurosci2011Smith RMSadee W18511691PubMedMeCP2, a key contributor to neurological disease, activates and represses transcription.Science2008Chahrour MJung SYShaw CZhou XWong STQin JZoghbi HY20392956PubMedRett syndrome microglia damage dendrites and synapses by the elevated release of glutamate.J Neurosci2010Maezawa IJin LW16613900PubMedIdentification of cis-regulatory elements for MECP2 expression.Hum Mol Genet2006Liu JFrancke U20368621PubMedCross talk between microRNA and epigenetic regulation in adult neurogenesis.J Cell Biol2010Szulwach KELi XSmrt RDLi YLuo YLin LSantistevan NJLi WZhao XJin P21070191PubMedA brain-derived MeCP2 complex supports a role for MeCP2 in RNA processing.Biosci Rep2011Long SWOoi JYYau PMJones PL18203756PubMedMeCP2-dependent repression of an imprinted miR-184 released by depolarization.Hum Mol Genet2008Nomura TKimura MHorii TMorita SSoejima HKudo SHatada I20452318PubMedEpigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation.Cell Stem Cell2010Liu CTeng ZQSantistevan NJSzulwach KEGuo WJin PZhao X24069510PubMedIdentification of TET1 Partners That Control Its DNA-Demethylating Function.Genes Cancer2013Cartron PFNadaradjane ALepape FLalier LGardie BVallette FM17573714PubMedMicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11).Biochemistry (Mosc)2007Burmistrova OAGoltsov AYAbramova LIKaleda VGOrlova VARogaev EI16251272PubMedRegulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2.Proc Natl Acad Sci U S A2005Young JIHong EPCastle JCCrespo-Barreto JBowman ABRose MFKang DRichman RJohnson JMBerget SZoghbi HY23431031PubMedHuman-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p.Genes Dev2013Han KGennarino VALee YPang KHashimoto-Torii KChoufani SRaju CSOldham MCWeksberg RRakic PLiu ZZoghbi HY23960241PubMedMicroRNA-mediated epigenetic silencing of sirtuin1 contributes to impaired angiogenic responses.Circ Res2013Volkmann IKumarswamy RPfaff NFiedler JDangwal SHolzmann ABatkai SGeffers RLother AHein LThum T22615490PubMedPhosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation.Mol Cell Biol2012Gonzales MLAdams SDunaway KWLaSalle JM25458568PubMedTranscriptional regulation of GAD1 GABA synthesis gene in the prefrontal cortex of subjects with schizophrenia.Schizophr Res2014Mitchell ACJiang YPeter CAkbarian S22141737PubMedChronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures.Alcohol Clin Exp Res2012Guo YChen YCarreon SQiang M24615633PubMedRett syndrome and MeCP2.Neuromolecular Med2014Liyanage VRRastegar M24916645PubMedGluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells.Eur J Hum Genet2015Livide GPatriarchi TAmenduni MAmabile SYasui DCalcagno ELo Rizzo CDe Falco GUlivieri CAriani FMari FMencarelli MAHell JWRenieri AMeloni Idisease pathwayPW:0000013Pathway Ontology22334035PubMedDownregulation of CNPase in a MeCP2 deficient mouse model of Rett syndromeNeurol Res2012Wu WGu WXu XShang SZhao Z23611944PubMedDysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.RNA Biol2013Petazzi PSandoval JSzczesna KJorge OCRoa LSayols SGomez AHuertas DEsteller M20716963PubMedDisrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome.Epigenetics2010Urdinguio RGFernandez AFLopez-Nieva PRossi SHuertas DKulis MLiu CGCroce CMCalin GAEsteller MRett syndromeDOID:1206Disease20400852PubMedAlternative polyadenylation of MeCP2: Influence of cis-acting elements and trans-acting factors.RNA Biol2010Newnham CMHall-Pogar TLiang SWu JTian BHu JLutz CS20010955PubMedIschemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.J Cereb Blood Flow Metab2010Lusardi TAFarr CDFaulkner CLPignataro GYang TLan JSimon RPSaugstad JA23770565PubMedRett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor.Nat Neurosci2013Lyst MJEkiert REbert DHMerusi CNowak JSelfridge JGuy JKastan NRRobinson NDde Lima Alves FRappsilber JGreenberg MEBird A18820302PubMedMECP2 genomic structure and function: insights from ENCODE.Nucleic Acids Res2008Singh JSaxena AChristodoulou JRavine D20697302PubMedA novel transcriptional regulator of myelin gene expression: implications for neurodevelopmental disorders.Neuroreport2010Vora PMina RNamaka MFrost EE21212100PubMedReduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model.Hum Mol Genet2011Ricciardi SBoggio EMGrosso SLonetti GForlani GStefanelli GCalcagno EMorello NLandsberger NBiffo SPizzorusso TGiustetto MBroccoli V