Mecp2 and associated Rett syndrome (Mus musculus)

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10Activation complexDNA condensingAstrocytesMicro RNA regulationcofactorsMecp2 associated diseases:- RETT-syndrome- schizophrenia- FASD (fetal alcohol syndrome)- PPM-X-syndrome- autism- Prader-Will-syndrome- Angelman-syndrometrimethyl lysine 27Repressor complexformation byphosphorylation of Mecp2 Effects on other cells than neuronsPOligodendrocytesrepressed by Mecp2DNA bindingtranscriptional regulation by Mecp2Chromatin structure maintenanceMecp2 affects:- all cell types, especially neurons, astrocytes, oligodendrocytes and glial cells- neuronal differentiation- neuronal maturation- neuronal function- neuronal morphology- synaptic plasticityalternative splicing of:Microglia101011miR-221Dlx5miR-146aAk081227miR-296miR-130miR-122aNcor1H3Mecp2YB1Tet1Ak087060Mef2cmiR-221miR-197GlutamatemiR-199miR-146bPRPF3BdnfNf1CdonGamtmiR-187miR-409Smc3Apoc2Ezh2NR1HB1miR-137GAD1HP1MagSstFut8NrepmiR-199bmiR-29bmiR-342miR-329Sin3aGprin1MbpmiR-184CNPasemiR-193amiR-92Oprk1Csrp1miR-222GABAA2bp1Fgf2miR-3829, 131513, 16146, 1315157313758151257101577108101151571010151041515152activated by Mecp2, mostprobably through DNAmethylation control151215105YB112Creb1Mecp2Mecp2Mecp2


Description

Mecp2 is in many mammals an important regulator of neuronal function and development. 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, and PPM-X-syndrome. Dependant on the cofactors Mecp2 acts as an activator or repressor of transcription and micro RNA production. It influences 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.

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
129303view13:46, 26 March 2024MkutmonOntology Term : 'disease pathway' added !
120273view12:55, 23 November 2021EgonwReplaces a PMCID with a PMID
117915view10:34, 23 May 2021EweitzModified title
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 (http://www.ncbi.nlm.nih.gov/pubmed/19897480)
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

DataNodes

View all...
NameTypeDatabase referenceComment
A2bp1GeneProductENSMUSG00000008658 (Ensembl) ataxin 2 binding protein 1
Ak081227GeneProduct
Ak087060GeneProduct
Apoc2GeneProductENSMUSG00000002992 (Ensembl) apolipoprotein C-II
BdnfGeneProductENSMUSG00000048482 (Ensembl) brain derived neurotrophic factor
CNPaseGeneProductENSMUSG00000006782 (Ensembl) 2',3'-cyclic nucleotide 3' phosphodiesterase
CdonGeneProductENSMUSG00000038119 (Ensembl) cell adhesion molecule-related/down-regulated by oncogenes
Creb1GeneProduct
Csrp1GeneProductENSMUSG00000026421 (Ensembl) cysteine and glycine-rich protein 1
Dlx5GeneProductENSMUSG00000029755 (Ensembl)
  • distal-less homeobox 5
  • controls GABA production
Ezh2GeneProductENSMUSG00000029687 (Ensembl) histone H3 lysine 27 methyltransferase
Fgf2GeneProduct
Fut8GeneProduct
GABAMetabolite16865 (ChEBI)
GAD1GeneProductENSMUSG00000070880 (Ensembl)
GamtGeneProductENSMUSG00000020150 (Ensembl) guanidinoacetate methyltransferase
GlutamateMetabolite29987 (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
HP1GeneProduct
MagGeneProductENSMUSG00000036634 (Ensembl) myelin-associated glycoprotein
MbpGeneProductENSMUSG00000041607 (Ensembl) myelin basic protein
Mecp2GeneProductENSMUSG00000031393 (Ensembl) methyl CpG binding protein 2
Mef2cGeneProductENSMUSG00000005583 (Ensembl) myocyte enhancer factor 2C
NR1GeneProduct
  • related to FASD (fetal alcohole spectrum disorder)
  • NMDA receptor subunit
Ncor1GeneProductENSMUSG00000018501 (Ensembl) nuclear receptor co-repressor 1
Nf1GeneProduct
NrepGeneProductENSMUSG00000042834 (Ensembl) neuronal regeneration related protein
Oprk1GeneProductENSMUSG00000025905 (Ensembl) opioid receptor, kappa 1
PRPF3GeneProductENSMUSG00000015748 (Ensembl) PRP3 pre-mRNA processing factor 3 homolog (yeast)
Sin3aGeneProductENSMUSG00000042557 (Ensembl)
Smc3GeneProductENSMUSG00000024974 (Ensembl) tructural maintenance of chromosomes 3
SstGeneProductENSMUSG00000004366 (Ensembl) Somatostatin
Tet1GeneProductENSMUSG00000047146 (Ensembl) tet methylcytosine dioxygenase 1
YB1GeneProductdata obtained with human cell line and mouse primary tissue
miR-122aRnaMIMAT0000246 (miRBase mature sequence)
miR-130RnaMI0000156 (miRBase Sequence) Base sequence! It is unclear which mature miRNA was tested.
miR-137RnaMIMAT0016986 (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
miR-146aRnamiR-146a (miRBase mature sequence)
miR-146bRnaMIMAT0004826 (miRBase mature sequence)
miR-184RnaMIMAT0000213 (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
miR-187RnaMIMAT0016997 (miRBase mature sequence) no connection between Mecp2 and miR-187 in other sources than [3]
miR-193aRnaMIMAT0004544 (miRBase mature sequence)
miR-197RnaMI0005485 (miRBase mature sequence)
miR-199RnaMIMAT0000230 (miRBase mature sequence)
miR-199bRnaMIMAT0000672 (miRBase mature sequence)
miR-221RnaMIMAT0017060 (miRBase mature sequence)
miR-222RnaMIMAT0017061 (miRBase mature sequence)
miR-296RnaMIMAT0000374 (miRBase mature sequence)
miR-29bRnaMIMAT0004523 (miRBase mature sequence)
miR-329RnaMIMAT0017032 (miRBase mature sequence)
miR-342RnaMIMAT0000590 (miRBase mature sequence)
miR-382RnaMIMAT0004691 (miRBase mature sequence)
miR-409RnaMIMAT0001090 (miRBase mature sequence)
miR-92RnaMIMAT0000539 (miRBase mature sequence)

Annotated Interactions

No annotated interactions

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