Mecp2 and Associated Rett Syndrome (Mus musculus)

From WikiPathways

Revision as of 14:29, 17 September 2019 by MaintBot (Talk | contribs)
(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)
Jump to: navigation, search
1Activation complexmicro RNA regulationmiRNAtrimethyl lysine 27Cis-Regulatory ElementsNMDA receptorregulation by miRNA(mostly posttranscriptional repression)Oligodendrocytescell proliferationlong noncoding RNA regulationlncRNAGABA-receptorEffects on other cells than neuronsDNA bindingmacropinocytosisPTrans-regulator Elementsstimulate/inhibit by Polyadenylation of Mecp2transcriptional regulation of Mecp2transcriptional regulation by Mecp2DNA condensingAstrocytesRepressor complex formation byphosphorylation of Mecp2 Microgliaalternative splicing of:repressed by Mecp2cofactorsPromotor elements4mmu-miR-146a-5pmmu-miR-329-5pSmc3Brn2MYT1MagHP1Csrp1Ncor1Gprin1CNPaseOprk1Fgf3RESTmmu-miR-199a-3p GAD1TAF1Fgf2mmu-miR-146b-3pmmu-miR-29b-1-5p mmu-miR-122-5pDlx5Nf1mmu-miR-296-5pAk087060MbpBrn3mmu-miR-193a-5p mmu-miR-221-5pmmu-miR-382-3pmmu-miR-130a-3pPRPF3BdnfNR1/GRIN1mmu-miR-152-5pmmu-miR-342-3p GABAFgf5Fut8SP3Mef2cCdonmmu-miR-92a-3pmmu-miR-30a-3p BCL6HB1mmu-miR-130bmmu-miR-222-5pAk081227GlutamateSin3ammu-miR-137-5p Apoc2Nrepmmu-miR-199a-3p Fgf4YB1Arhgef26mmu-miR-409-3p Mecp2mmu-miR-184-3pmmu-miR-483-5p mmu-miR-132-5p mmu-miR-187-5pH3mmu-miR-221-5pSP1Tet1Ezh2hnRNP FCTCFSstGabrr2C/EBPGamtA2bp1hnRNP HMYT1E2F1mmu-miR-199b-5pTAP111523171711911118101711516177, 91177activated by Mecp21751717185619125217, 129151117201919247, 1417172018516112171222611016113211615192511181731YB19, 25Creb1Mecp2Mecp2Mecp2SP111, 19


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. The pathway is demonstrated for mouse but as the genes are highly conserved in mammals, many of these are valid for human, too.

Quality Tags

Ontology Terms



View all...
  1. Liyanage VR, Rastegar M; ''Rett syndrome and MeCP2.''; Neuromolecular Med, 2014 PubMed Europe PMC Scholia
  2. Smith RM, Sadee W; ''Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.''; Front Synaptic Neurosci, 2011 PubMed Europe PMC Scholia
  3. Cartron PF, Nadaradjane A, Lepape F, Lalier L, Gardie B, Vallette FM; ''Identification of TET1 Partners That Control Its DNA-Demethylating Function.''; Genes Cancer, 2013 PubMed Europe PMC Scholia
  4. Dag H Yasui, Huichun Xu, Keith W Dunaway, Janine M LaSalle, Lee-Way Jin, Izumi Maezawa; ''MeCP2 modulates gene expression pathways in astrocytes''; Mol Autism, 2013 PubMed Europe PMC Scholia
  5. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY; ''''; , PubMed Europe PMC Scholia
  6. Long SW, Ooi JY, Yau PM, Jones PL; ''A brain-derived MeCP2 complex supports a role for MeCP2 in RNA processing.''; Biosci Rep, 2011 PubMed Europe PMC Scholia
  7. Nomura T, Kimura M, Horii T, Morita S, Soejima H, Kudo S, Hatada I; ''MeCP2-dependent repression of an imprinted miR-184 released by depolarization.''; Hum Mol Genet, 2008 PubMed Europe PMC Scholia
  8. Maezawa I, Jin LW; ''Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate.''; J Neurosci, 2010 PubMed Europe PMC Scholia
  9. Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, Kang D, Richman R, Johnson JM, Berget S, Zoghbi HY; ''Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2.''; Proc Natl Acad Sci U S A, 2005 PubMed Europe PMC Scholia
  10. Vora P, Mina R, Namaka M, Frost EE; ''A novel transcriptional regulator of myelin gene expression: implications for neurodevelopmental disorders.''; Neuroreport, 2010 PubMed Europe PMC Scholia
  11. Singh J, Saxena A, Christodoulou J, Ravine D; ''MECP2 genomic structure and function: insights from ENCODE.''; Nucleic Acids Res, 2008 PubMed Europe PMC Scholia
  12. Liu C, Teng ZQ, Santistevan NJ, Szulwach KE, Guo W, Jin P, Zhao X; ''Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation.''; Cell Stem Cell, 2010 PubMed Europe PMC Scholia
  13. Han K, Gennarino VA, Lee Y, Pang K, Hashimoto-Torii K, Choufani S, Raju CS, Oldham MC, Weksberg R, Rakic P, Liu Z, Zoghbi HY; ''Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p.''; Genes Dev, 2013 PubMed Europe PMC Scholia
  14. Mitchell AC, Jiang Y, Peter C, Akbarian S; ''Transcriptional regulation of GAD1 GABA synthesis gene in the prefrontal cortex of subjects with schizophrenia.''; Schizophr Res, 2014 PubMed Europe PMC Scholia
  15. Lusardi TA, Farr CD, Faulkner CL, Pignataro G, Yang T, Lan J, Simon RP, Saugstad JA; ''Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.''; J Cereb Blood Flow Metab, 2010 PubMed Europe PMC Scholia
  16. Petazzi P, Sandoval J, Szczesna K, Jorge OC, Roa L, Sayols S, Gomez A, Huertas D, Esteller M; ''Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.''; RNA Biol, 2013 PubMed Europe PMC Scholia
  17. Urdinguio RG, Fernandez AF, Lopez-Nieva P, Rossi S, Huertas D, Kulis M, Liu CG, Croce CM, Calin GA, Esteller M; ''Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome.''; Epigenetics, 2010 PubMed Europe PMC Scholia
  18. Szulwach KE, Li X, Smrt RD, Li Y, Luo Y, Lin L, Santistevan NJ, Li W, Zhao X, Jin P; ''Cross talk between microRNA and epigenetic regulation in adult neurogenesis.''; J Cell Biol, 2010 PubMed Europe PMC Scholia
  19. Liu J, Francke U; ''Identification of cis-regulatory elements for MECP2 expression.''; Hum Mol Genet, 2006 PubMed Europe PMC Scholia
  20. Newnham CM, Hall-Pogar T, Liang S, Wu J, Tian B, Hu J, Lutz CS; ''Alternative polyadenylation of MeCP2: Influence of cis-acting elements and trans-acting factors.''; RNA Biol, 2010 PubMed Europe PMC Scholia
  21. Guo Y, Chen Y, Carreon S, Qiang M; ''Chronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures.''; Alcohol Clin Exp Res, 2012 PubMed Europe PMC Scholia
  22. Volkmann I, Kumarswamy R, Pfaff N, Fiedler J, Dangwal S, Holzmann A, Batkai S, Geffers R, Lother A, Hein L, Thum T; ''MicroRNA-mediated epigenetic silencing of sirtuin1 contributes to impaired angiogenic responses.''; Circ Res, 2013 PubMed Europe PMC Scholia
  23. Wu W, Gu W, Xu X, Shang S, Zhao Z; ''Downregulation of CNPase in a MeCP2 deficient mouse model of Rett syndrome''; Neurol Res, 2012 PubMed Europe PMC Scholia
  24. Lyst MJ, Ekiert R, Ebert DH, Merusi C, Nowak J, Selfridge J, Guy J, Kastan NR, Robinson ND, de Lima Alves F, Rappsilber J, Greenberg ME, Bird A; ''Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor.''; Nat Neurosci, 2013 PubMed Europe PMC Scholia
  25. Gonzales ML, Adams S, Dunaway KW, LaSalle JM; ''Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation.''; Mol Cell Biol, 2012 PubMed Europe PMC Scholia
  26. Burmistrova OA, Goltsov AY, Abramova LI, Kaleda VG, Orlova VA, Rogaev EI; ''MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11).''; Biochemistry (Mosc), 2007 PubMed Europe PMC Scholia


View all...
107202view14:29, 17 September 2019MaintBotChEBI identifier normalization
97545view14:40, 24 May 2018Mkutmonfixed microRNA linkouts
97541view14:33, 24 May 2018Mkutmonremove special character in comment
97524view14:10, 24 May 2018TeacupChanged miRBase mature sequence database to miRBase sequence
88904view08:39, 17 August 2016Fehrhartupdate
87766view10:00, 25 July 2016ElisaOntology Term : 'regulatory pathway' added !
87765view10:00, 25 July 2016ElisaOntology Term : 'regulatory pathway pertinent to the brain' added !
83562view09:04, 25 November 2015FehrhartUpdated miRNA names according to actual annotation rules
82621view09:16, 15 October 2015Fehrhartdeleted information from retracted paper (
81213view17:52, 4 August 2015KhanspersAdded annotation for Creb1
80241view05:32, 28 May 2015Khansperschanged color of miRNA nodes
79772view13:02, 15 April 2015FehrhartImplemented miR regulation of Mecp2
79749view08:41, 9 April 2015FehrhartModified description
79748view08:38, 9 April 2015FehrhartModification of description
79747view08:35, 9 April 2015FehrhartModified description
79743view14:48, 8 April 2015Fehrhartconnected lines
79742view14:43, 8 April 2015Fehrhartadded transcriptional regulation of Mecp2
79687view19:43, 4 April 2015AlexanderPicoModified title
79665view10:03, 2 April 2015FehrhartUpdate alternative splicing path
79656view14:47, 1 April 2015FehrhartlncRNA
79655view13:11, 1 April 2015FehrhartFinished miRNA annotation
79650view10:20, 1 April 2015Fehrhartstart updating miR regulation
79649view09:13, 1 April 2015FehrhartUpdate of transcriptional regulation
79639view16:45, 31 March 2015EgonwModified title
79638view14:08, 31 March 2015FehrhartModified description
79637view14:07, 31 March 2015FehrhartNew pathway

External references


View all...
NameTypeDatabase referenceComment
mmu-miR-122-5pRnaMIMAT0000246 (miRBase mature sequence)
A2bp1GeneProductENSMUSG00000008658 (Ensembl) ataxin 2 binding protein 1
Apoc2GeneProductENSMUSG00000002992 (Ensembl) apolipoprotein C-II
Arhgef26GeneProductENSMUSG00000036885 (Ensembl) Rho guanine nucleotide exchange factor (GEF) 26
BCL6GeneProductENSMUSG00000022508 (Ensembl) B cell leukemia/lymphoma 6
BdnfGeneProductENSMUSG00000048482 (Ensembl) brain derived neurotrophic factor
Brn2GeneProductENSMUSG00000095139 (Ensembl) POU domain, class 3, transcription factor 2
Brn3GeneProductENSMUSG00000048349 (Ensembl) POU domain, class 4, transcription factor 1
C/EBPGeneProductENSMUSG00000071637 (Ensembl) CCAAT/enhancer binding protein (Cebpd), delta
CNPaseGeneProductENSMUSG00000006782 (Ensembl) 2',3'-cyclic nucleotide 3' phosphodiesterase
CTCFGeneProductENSMUSG00000005698 (Ensembl) CCCTC-binding factor
CdonGeneProductENSMUSG00000038119 (Ensembl) cell adhesion molecule-related/down-regulated by oncogenes
Creb1GeneProductENSMUSG00000025958 (Ensembl)
Csrp1GeneProductENSMUSG00000026421 (Ensembl) cysteine and glycine-rich protein 1
Dlx5GeneProductENSMUSG00000029755 (Ensembl)
  • distal-less homeobox 5
  • controls GABA production
E2F1GeneProductENSMUSG00000027490 (Ensembl) E2F transcription factor 1
Ezh2GeneProductENSMUSG00000029687 (Ensembl) histone H3 lysine 27 methyltransferase
Fgf2GeneProductENSMUSG00000037225 (Ensembl) fibroblast growth factor 2
Fgf3GeneProductENSMUSG00000031074 (Ensembl) fibroblast growth factor 3
Fgf4GeneProductENSMUSG00000050917 (Ensembl)
Fut8GeneProductENSMUSG00000021065 (Ensembl) fucosyltransferase 8
GABAMetaboliteCHEBI:16865 (ChEBI)
GAD1GeneProductENSMUSG00000070880 (Ensembl)
Gabrr2GeneProductENSMUSG00000023267 (Ensembl) gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
GamtGeneProductENSMUSG00000020150 (Ensembl) guanidinoacetate methyltransferase
GlutamateMetaboliteCHEBI:29987 (ChEBI)
Gprin1GeneProductENSMUSG00000069227 (Ensembl) G protein-regulated inducer of neurite outgrowth 1
H3GeneProductHistone 3
HB1GeneProductchromatin factor, data obtained using human cell line and mouse primary tissue
MYT1GeneProductENSMUSG00000010505 (Ensembl) Myelin transcription factor 1
MagGeneProductENSMUSG00000036634 (Ensembl) myelin-associated glycoprotein
MbpGeneProductENSMUSG00000041607 (Ensembl) myelin basic protein
Mecp2GeneProductENSMUSG00000031393 (Ensembl) methyl CpG binding protein 2
Mef2cGeneProductENSMUSG00000005583 (Ensembl) myocyte enhancer factor 2C
NR1/GRIN1GeneProductENSMUSG00000026959 (Ensembl)
  • related to FASD (fetal alcohole spectrum disorder)
  • NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1
Ncor1GeneProductENSMUSG00000018501 (Ensembl) nuclear receptor co-repressor 1
Nf1GeneProductENSMUSG00000020716 (Ensembl) neurofibromatosis 1
NrepGeneProductENSMUSG00000042834 (Ensembl) neuronal regeneration related protein
Oprk1GeneProductENSMUSG00000025905 (Ensembl) opioid receptor, kappa 1
PRPF3GeneProductENSMUSG00000015748 (Ensembl) PRP3 pre-mRNA processing factor 3 homolog (yeast)
RESTGeneProductENSMUSG00000029249 (Ensembl)
  • RE1-silencing transcription factor
  • Silences Mecp2 in non-neuronal tissue
SP1GeneProductENSMUSG00000001280 (Ensembl) trans-acting transcription factor 1
SP3GeneProductENSMUSG00000027109 (Ensembl) trans-acting transcription factor 3
Sin3aGeneProductENSMUSG00000042557 (Ensembl)
Smc3GeneProductENSMUSG00000024974 (Ensembl) tructural maintenance of chromosomes 3
SstGeneProductENSMUSG00000004366 (Ensembl) Somatostatin
TAF1GeneProductENSMUSG00000031314 (Ensembl) TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor
TAP1GeneProductENSMUSG00000037321 (Ensembl) transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Tet1GeneProductENSMUSG00000047146 (Ensembl) tet methylcytosine dioxygenase 1
YB1GeneProductENSMUSG00000028639 (Ensembl)
  • data obtained with human cell line and mouse primary tissue
  • Y box protein 1
hnRNP FGeneProductENSMUSG00000042079 (Ensembl)
  • Hnrnpf
  • heterogeneous nuclear ribonucleoprotein F
hnRNP HGeneProductENSMUSG00000007850 (Ensembl) HNRNPH1
mmu-miR-130a-3pRnaMIMAT0000141 (miRBase mature sequence) Base sequence! It is unclear which mature miRNA was tested.
mmu-miR-130bRnaMIMAT0000387 (miRBase mature sequence)
  • reported for human only
  • binding site at 3'UTR of Mecp2 reported, regulative effect unclear
mmu-miR-132-5p RnaMIMAT0016984 (miRBase mature sequence)
mmu-miR-137-5p RnaMIMAT0016986 (miRBase mature sequence)
  • influences neuronal stem cell proliferation and differentiation
  • MeCP2 and Sox2 bind directly to the 5' regulatory region of miR-137 in aNSCs
mmu-miR-146a-5pRnaMIMAT0000158 (miRBase mature sequence)
mmu-miR-146b-3pRnaMIMAT0004826 (miRBase mature sequence)
mmu-miR-152-5pRnaMIMAT0016991 (miRBase mature sequence)
mmu-miR-184-3pRnaMIMAT0000213 (miRBase mature sequence) The 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-184
mmu-miR-187-5pRnaMIMAT0016997 (miRBase mature sequence) no connection between Mecp2 and miR-187 in other sources than [3]
mmu-miR-193a-5p RnaMIMAT0004544 (miRBase mature sequence)
mmu-miR-199a-3p RnaMIMAT0000230 (miRBase mature sequence)
mmu-miR-199b-5pRnaMIMAT0000672 (miRBase mature sequence)
mmu-miR-221-5pRnaMIMAT0017060 (miRBase mature sequence)
mmu-miR-222-5pRnaMIMAT0017061 (miRBase mature sequence)
mmu-miR-296-5pRnaMIMAT0000374 (miRBase mature sequence)
mmu-miR-29b-1-5pRnaMIMAT0004523 (miRBase mature sequence)
mmu-miR-30a-3p RnaMIMAT0000129 (miRBase mature sequence)
mmu-miR-329-5pRnaMIMAT0017032 (miRBase mature sequence)
mmu-miR-342-3p RnaMIMAT0000590 (miRBase mature sequence)
mmu-miR-382-3pRnaMIMAT0004691 (miRBase mature sequence)
mmu-miR-409-3p RnaMIMAT0001090 (miRBase mature sequence)
mmu-miR-483-5p RnaMIMAT0004782 (miRBase mature sequence)
mmu-miR-92a-3pRnaMIMAT0000539 (miRBase mature sequence)

Annotated Interactions

No annotated interactions

Personal tools