Mecp2 and Associated Rett Syndrome (Mus musculus)

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12Oligodendrocytestranscriptional regulation by Mecp2Trans-regulator Elementsstimulate/inhibit by Polyadenylation of Mecp2NMDA receptortranscriptional regulation of Mecp2Activation complexrepressed by Mecp2long noncoding RNA regulationlncRNAtrimethyl lysine 27Promotor elementscofactorsDNA condensingcell proliferationCis-Regulatory ElementsMicrogliaregulation by miRNA(mostly posttranscriptional repression)macropinocytosisAstrocytesalternative splicing of:GABA-receptorRepressor complex formation byphosphorylation of Mecp2 micro RNA regulationmiRNAPDNA bindingEffects on other cells than neurons25mmu-miR-146b-3pCTCFmmu-miR-187-5pOprk1mmu-miR-199a-3p MbpSP1Arhgef26Fut8Sstmmu-miR-29b-1-5pAk081227mmu-miR-130bmmu-miR-342-3p RESTCdonGprin1hnRNP Hmmu-miR-199a-3p NR1/GRIN1Gabrr2MYT1mmu-miR-329-5pGamtSP3Brn2BCL6H3 mmu-miR-122-5pDlx5Sin3aGlutamateMecp2Brn3HB1Ncor1TAF1Mef2cmmu-miR-409-3p mmu-miR-221-5pMagEzh2MYT1A2bp1Fgf2HP1mmu-miR-222-5pSmc3Fgf4mmu-miR-130a-3pmmu-miR-184-3pE2F1Nf1Apoc2YB1NrepTet1TAP1mmu-miR-152-5pmmu-miR-382-3pmmu-miR-221-5pmmu-miR-199b-5pPRPF3CNPasemmu-miR-30a-3p mmu-miR-92a-3pFgf3Bdnfmmu-miR-296-5pC/EBPmmu-miR-193a-5p GABAAk087060mmu-miR-132-5p Csrp1Fgf5hnRNP Fmmu-miR-483-5p mmu-miR-137-5p GAD1mmu-miR-146a-5p4881012416421211216811, 1323121811224121215484activated by Mecp21294121241481824412716124222012212121726812151611, 1912471811, 174632141212261624YB17, 17Creb1Mecp2Mecp2Mecp2SP116, 18


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.

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  1. 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
  2. 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
  3. 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
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  8. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY; ''''; , PubMed
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  11. 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
  12. Liyanage VR, Rastegar M; ''Rett syndrome and MeCP2.''; Neuromolecular Med, 2014 PubMed
  13. 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
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  26. 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


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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


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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
GABAMetabolite16865 (ChEBI)
GAD1GeneProductENSMUSG00000070880 (Ensembl)
Gabrr2GeneProductENSMUSG00000023267 (Ensembl) gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
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
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

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