MECP2 and Associated Rett Syndrome (Homo sapiens)

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Description

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

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Bibliography

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  1. 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
  2. Smith RM, Sadee W; ''Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.''; Front Synaptic Neurosci, 2011 PubMed
  3. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY; ''MeCP2, a key contributor to neurological disease, activates and represses transcription.''; Science, 2008 PubMed
  4. Maezawa I, Jin LW; ''Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate.''; J Neurosci, 2010 PubMed
  5. Liu J, Francke U; ''Identification of cis-regulatory elements for MECP2 expression.''; Hum Mol Genet, 2006 PubMed
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  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
  14. 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
  15. 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
  16. 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
  17. 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
  18. Liyanage VR, Rastegar M; ''Rett syndrome and MeCP2.''; Neuromolecular Med, 2014 PubMed
  19. Livide G, Patriarchi T, Amenduni M, Amabile S, Yasui D, Calcagno E, Lo Rizzo C, De Falco G, Ulivieri C, Ariani F, Mari F, Mencarelli MA, Hell JW, Renieri A, Meloni I; ''GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells.''; Eur J Hum Genet, 2015 PubMed
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. Singh J, Saxena A, Christodoulou J, Ravine D; ''MECP2 genomic structure and function: insights from ENCODE.''; Nucleic Acids Res, 2008 PubMed
  27. Vora P, Mina R, Namaka M, Frost EE; ''A novel transcriptional regulator of myelin gene expression: implications for neurodevelopmental disorders.''; Neuroreport, 2010 PubMed
  28. Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G, Calcagno E, Morello N, Landsberger N, Biffo S, Pizzorusso T, Giustetto M, Broccoli V; ''Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model.''; Hum Mol Genet, 2011 PubMed


History

View all...
CompareRevisionActionTimeUserComment
91190view05:20, 18 January 2017Khanspersupdated xref for mir-130a
91168view21:09, 14 January 2017AlexanderPicoQuick edit to datanode annotation or property
91157view07:23, 13 January 2017FehrhartQuick edit to datanode annotation or property
91156view07:21, 13 January 2017FehrhartQuick edit to datanode annotation or property
91155view22:41, 12 January 2017Khanspersupdated xref for PI3K/MAPK pathway
90609view13:50, 1 December 2016FehrhartModified description
88836view13:21, 15 August 2016Fehrhartconnected unconnected lines
88439view08:53, 8 August 2016Mkutmonfix publication reference
88226view13:03, 1 August 2016FehrhartCorrected citation (wrong pubmed ID)of GAMT and BDNF
87880view12:16, 25 July 2016RyanmillerOntology Term : 'disease pathway' added !
86084view14:09, 29 June 2016Fehrhartadded stimulation of MECP2 phosphorylation by neurotransmitters
86083view13:58, 29 June 2016Fehrhartadded transcription activation pathway
86068view23:38, 28 June 2016KhanspersOntology Term : 'Rett syndrome' added !
85537view09:30, 27 May 2016Fehrhartcorrection of typo
85536view09:28, 27 May 2016FehrhartAdded list of up and downregulated genes and metabolites
85535view09:15, 27 May 2016FehrhartUpdate epigenetic regulation of MECP2
85534view08:01, 27 May 2016FehrhartUpdate of gene names
84776view14:48, 18 March 2016FehrhartModified description
84025view18:50, 11 January 2016Khanspersremoved comment for hsa-miR-137, which caused character encoding issues
83577view07:08, 26 November 2015EgonwReplaced the PubMed Central ID with a PubMed ID.
83563view09:33, 25 November 2015FehrhartFinished miRNA and transregulator elements - pathway is now ready to work with
83541view15:37, 23 November 2015FehrhartModified description
83540view14:00, 23 November 2015Fehrharttransfer from M.musculus pathway complete except miRNA and long non-coding RNA
83539view13:19, 23 November 2015FehrhartNew pathway

External references

Datanodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AMPAGeneProductENSG00000155511 (Ensembl) Glutamate receptor
APOC2GeneProductENSG00000234906 (Ensembl) apolipoprotein C-II
ARHGEF26GeneProductENSG00000114790 (Ensembl) Rho guanine nucleotide exchange factor (GEF) 26
Ak081227GeneProduct
Ak087060GeneProduct
BCL6GeneProductENSG00000113916 (Ensembl) B cell leukemia/lymphoma 6
BDNFGeneProductENSG00000176697 (Ensembl) brain derived neurotrophic factor
BRN2GeneProductENSG00000184486 (Ensembl) POU domain, class 3, transcription factor 2
BRN3GeneProductENSG00000152192 (Ensembl) POU domain, class 4, transcription factor 1
C/EBPGeneProductENSG00000221869 (Ensembl) CCAAT/enhancer binding protein (Cebpd), delta
CAMK2AGeneProductENSG00000070808 (Ensembl)
CDONGeneProductENSG00000064309 (Ensembl) cell adhesion molecule-related/down-regulated by oncogenes
CNPGeneProductENSG00000173786 (Ensembl) 2',3'-cyclic nucleotide 3' phosphodiesterase
CREB1GeneProductENSG00000118260 (Ensembl)
CSRP1GeneProductENSG00000159176 (Ensembl) cysteine and glycine-rich protein 1
CTCFGeneProductENSG00000102974 (Ensembl) CCCTC-binding factor
Cytosine methylation PathwayWP3585 (WikiPathways)
DLX5GeneProductENSG00000105880 (Ensembl)
  • distal-less homeobox 5
  • controls GABA production
DLX6GeneProductENSG00000006377 (Ensembl)
DopamineMetaboliteHMDB00073 (HMDB)
E2F1GeneProductENSG00000101412 (Ensembl) E2F transcription factor 1
EZH2GeneProductENSG00000106462 (Ensembl) histone H3 lysine 27 methyltransferase
FGF2GeneProductENSG00000138685 (Ensembl) fibroblast growth factor 2
FGF3GeneProductENSG00000186895 (Ensembl) fibroblast growth factor 3
FGF4GeneProductENSG00000075388 (Ensembl)
FGF5GeneProductENSG00000138675 (Ensembl)
FKBP5GeneProductENSG00000096060 (Ensembl)
FUT8GeneProductENSG00000033170 (Ensembl) fucosyltransferase 8
GABAMetabolite16865 (ChEBI)
GABRR2GeneProductENSG00000111886 (Ensembl) gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
GAD1GeneProductENSG00000128683 (Ensembl)
GAMTGeneProductENSG00000130005 (Ensembl) guanidinoacetate methyltransferase
GPRIN1GeneProductENSG00000169258 (Ensembl) G protein-regulated inducer of neurite outgrowth 1
GRID1GeneProductENSG00000182771 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
  • related to FASD (fetal alcohole spectrum disorder)
  • NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1
GlutamateMetabolite29987 (ChEBI)
H3GeneProductHistone 3
HB1GeneProductchromatin factor, data obtained using human cell line and mouse primary tissue
HDAC1GeneProductENSG00000116478 (Ensembl)
HNRNPFGeneProductENSG00000169813 (Ensembl)
  • Hnrnpf
  • heterogeneous nuclear ribonucleoprotein F
HNRNPH1GeneProductENSG00000169045 (Ensembl) HNRNPH1
HP1GeneProduct
IGF2GeneProductENSG00000167244 (Ensembl)
MAGGeneProductENSG00000105695 (Ensembl) myelin-associated glycoprotein
MBPGeneProductENSG00000197971 (Ensembl) myelin basic protein
MECP2GeneProductENSG00000169057 (Ensembl) methyl CpG binding protein 2
MEF2CGeneProductENSG00000081189 (Ensembl) myocyte enhancer factor 2C
MPP1GeneProductENSG00000130830 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYT1GeneProductENSG00000196132 (Ensembl) Myelin transcription factor 1
MelatoninMetaboliteHMDB01389 (HMDB)
MyoinositolMetaboliteHMDB00211 (HMDB)
NCOR1GeneProductENSG00000141027 (Ensembl) nuclear receptor co-repressor 1
NF1GeneProductENSG00000196712 (Ensembl) neurofibromatosis 1
NMDAMetaboliteHMDB02393 (HMDB) N-Methyl-D-aspartic acid
NREPGeneProductENSG00000134986 (Ensembl) neuronal regeneration related protein
NorepinephrineMetaboliteHMDB00216 (HMDB)
OPRK1GeneProductENSG00000082556 (Ensembl) opioid receptor, kappa 1
PI3K/MAPK PathwayWP382 (WikiPathways)
PRPF3GeneProductENSG00000134748 (Ensembl) PRP3 pre-mRNA processing factor 3 homolog (yeast)
RBFOX1GeneProductENSG00000078328 (Ensembl) ataxin 2 binding protein 1, Rbfox1
RESTGeneProductENSG00000084093 (Ensembl)
  • RE1-silencing transcription factor
  • Silences Mecp2 in non-neuronal tissue
RPS6GeneProductENSG00000137154 (Ensembl)
SGK1GeneProductENSG00000118515 (Ensembl)
SIN3AGeneProductENSG00000169375 (Ensembl)
SMC3GeneProductENSG00000108055 (Ensembl) tructural maintenance of chromosomes 3
SP1GeneProductENSG00000185591 (Ensembl) trans-acting transcription factor 1
SP3GeneProductENSG00000172845 (Ensembl) trans-acting transcription factor 3
SSTGeneProductENSG00000157005 (Ensembl) Somatostatin
SerotoninMetaboliteHMDB00259 (HMDB)
TAF1GeneProductENSG00000147133 (Ensembl) TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor
TAP1GeneProductENSG00000168394 (Ensembl) transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
TET1GeneProductENSG00000138336 (Ensembl) tet methylcytosine dioxygenase 1
TET2GeneProductENSG00000168769 (Ensembl)
TET3GeneProductENSG00000187605 (Ensembl)
UBE3AGeneProductENSG00000114062 (Ensembl)
YB1GeneProductENSG00000065978 (Ensembl)
  • data obtained with human cell line and mouse primary tissue
  • Y box protein 1
hsa-miR-122-5pRnaMIMAT0000421 (miRBase mature sequence)
hsa-miR-130aRnaMIMAT0000425 (miRBase mature sequence) Base sequence! It is unclear which mature miRNA was tested.
hsa-miR-130b-3pRnaMIMAT0000691 (miRBase mature sequence)
  • reported for human only
  • binding site at 3'UTR of Mecp2 reported, regulative effect unclear
hsa-miR-132-5pRnaMIMAT0004594 (miRBase mature sequence)
hsa-miR-137RnaMIMAT0000429 (miRBase mature sequence) influences neuronal stem cell proliferation and differentiation
hsa-miR-146a-5p RnaMIMAT0000449 (miRBase mature sequence)
hsa-miR-146b-3p RnaMIMAT0004766 (miRBase mature sequence)
hsa-miR-152-3p RnaMIMAT0000438 (miRBase mature sequence)
hsa-miR-184 RnaMIMAT0000454 (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
hsa-miR-187-5p RnaMIMAT0004561 (miRBase mature sequence) no connection between Mecp2 and miR-187 in other sources than [3]
hsa-miR-193a-5p RnaMIMAT0004614 (miRBase mature sequence)
hsa-miR-197-3p RnaMIMAT0000227 (miRBase mature sequence)
hsa-miR-199a-3pRnaMIMAT0000232 (miRBase mature sequence)
hsa-miR-199a-5pRnaMIMAT0000231 (miRBase mature sequence)
hsa-miR-199b-5p RnaMIMAT0000263 (miRBase mature sequence)
hsa-miR-221-3pRnaMIMAT0000278 (miRBase mature sequence)
hsa-miR-221-5pRnaMIMAT0004568 (miRBase mature sequence)
hsa-miR-222-3pRnaMIMAT0000279 (miRBase mature sequence)
hsa-miR-296-5pRnaMIMAT0000690 (miRBase mature sequence)
hsa-miR-29b-1-5p RnaMIMAT0004514 (miRBase mature sequence)
hsa-miR-30a-3p RnaMIMAT0000088 (miRBase mature sequence) reported for human umbilical vein endothelial cells only
hsa-miR-329-5pRnaMIMAT0026555 (miRBase mature sequence)
hsa-miR-342-3pRnaMIMAT0000753 (miRBase mature sequence)
hsa-miR-382-3pRnaMIMAT0022697 (miRBase mature sequence)
hsa-miR-409-3pRnaMIMAT0001639 (miRBase mature sequence)
hsa-miR-483-5pRnaMIMAT0004761 (miRBase mature sequence) inhibition of Mecp2 expression only reported for human!
hsa-miR-92a-3p RnaMIMAT0000092 (miRBase mature sequence)

Annotated Interactions

No annotated interactions

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