Mecp2 and associated Rett syndrome (Mus musculus)
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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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- Liyanage VR, Rastegar M; ''Rett syndrome and MeCP2.''; Neuromolecular Med, 2014 PubMed Europe PMC Scholia
- Smith RM, Sadee W; ''Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.''; Front Synaptic Neurosci, 2011 PubMed Europe PMC Scholia
- 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
- 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
- Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY; ''''; , PubMed Europe PMC Scholia
- 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
- 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
- Maezawa I, Jin LW; ''Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate.''; J Neurosci, 2010 PubMed Europe PMC Scholia
- 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
- 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
- Singh J, Saxena A, Christodoulou J, Ravine D; ''MECP2 genomic structure and function: insights from ENCODE.''; Nucleic Acids Res, 2008 PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Liu J, Francke U; ''Identification of cis-regulatory elements for MECP2 expression.''; Hum Mol Genet, 2006 PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
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- 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
- 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
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
A2bp1 | GeneProduct | ENSMUSG00000008658 (Ensembl) | ataxin 2 binding protein 1 |
Ak081227 | GeneProduct | ||
Ak087060 | GeneProduct | ||
Apoc2 | GeneProduct | ENSMUSG00000002992 (Ensembl) | apolipoprotein C-II |
Arhgef26 | GeneProduct | ENSMUSG00000036885 (Ensembl) | Rho guanine nucleotide exchange factor (GEF) 26 |
Bdnf | GeneProduct | ENSMUSG00000048482 (Ensembl) | brain derived neurotrophic factor |
CNPase | GeneProduct | ENSMUSG00000006782 (Ensembl) | 2',3'-cyclic nucleotide 3' phosphodiesterase |
Cdon | GeneProduct | ENSMUSG00000038119 (Ensembl) | cell adhesion molecule-related/down-regulated by oncogenes |
Creb1 | GeneProduct | ||
Csrp1 | GeneProduct | ENSMUSG00000026421 (Ensembl) | cysteine and glycine-rich protein 1 |
Dlx5 | GeneProduct | ENSMUSG00000029755 (Ensembl) |
|
Ezh2 | GeneProduct | ENSMUSG00000029687 (Ensembl) | histone H3 lysine 27 methyltransferase |
Fgf2 | GeneProduct | ||
Fut8 | GeneProduct | ||
GABA | Metabolite | 16865 (ChEBI) | |
GAD1 | GeneProduct | ENSMUSG00000070880 (Ensembl) | |
Gabrr2 | GeneProduct | ENSMUSG00000023267 (Ensembl) | gamma-aminobutyric acid (GABA) C receptor, subunit rho 2 |
Gamt | GeneProduct | ENSMUSG00000020150 (Ensembl) | guanidinoacetate methyltransferase |
Glutamate | Metabolite | 29987 (ChEBI) | |
Gprin1 | GeneProduct | ENSMUSG00000069227 (Ensembl) | G protein-regulated inducer of neurite outgrowth 1 |
H3 | GeneProduct | Histone 3 | |
HB1 | GeneProduct | chromatin factor, data obtained using human cell line and mouse primary tissue | |
HP1 | GeneProduct | ||
Mag | GeneProduct | ENSMUSG00000036634 (Ensembl) | myelin-associated glycoprotein |
Mbp | GeneProduct | ENSMUSG00000041607 (Ensembl) | myelin basic protein |
Mecp2 | GeneProduct | ENSMUSG00000031393 (Ensembl) | methyl CpG binding protein 2 |
Mef2c | GeneProduct | ENSMUSG00000005583 (Ensembl) | myocyte enhancer factor 2C |
NR1 | GeneProduct |
| |
Ncor1 | GeneProduct | ENSMUSG00000018501 (Ensembl) | nuclear receptor co-repressor 1 |
Nf1 | GeneProduct | ||
Nrep | GeneProduct | ENSMUSG00000042834 (Ensembl) | neuronal regeneration related protein |
Oprk1 | GeneProduct | ENSMUSG00000025905 (Ensembl) | opioid receptor, kappa 1 |
PRPF3 | GeneProduct | ENSMUSG00000015748 (Ensembl) | PRP3 pre-mRNA processing factor 3 homolog (yeast) |
Sin3a | GeneProduct | ENSMUSG00000042557 (Ensembl) | |
Smc3 | GeneProduct | ENSMUSG00000024974 (Ensembl) | tructural maintenance of chromosomes 3 |
Sst | GeneProduct | ENSMUSG00000004366 (Ensembl) | Somatostatin |
Tet1 | GeneProduct | ENSMUSG00000047146 (Ensembl) | tet methylcytosine dioxygenase 1 |
YB1 | GeneProduct | data obtained with human cell line and mouse primary tissue | |
miR-122a | Rna | MIMAT0000246 (miRBase mature sequence) | |
miR-130 | Rna | MI0000156 (miRBase Sequence) | Base sequence! It is unclear which mature miRNA was tested. |
miR-137 | Rna | MIMAT0016986 (miRBase mature sequence) |
|
miR-146a | Rna | miR-146a (miRBase mature sequence) | |
miR-146b | Rna | MIMAT0004826 (miRBase mature sequence) | |
miR-184 | Rna | MIMAT0000213 (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-187 | Rna | MIMAT0016997 (miRBase mature sequence) | no connection between Mecp2 and miR-187 in other sources than [3] |
miR-193a | Rna | MIMAT0004544 (miRBase mature sequence) | |
miR-197 | Rna | MI0005485 (miRBase mature sequence) | |
miR-199 | Rna | MIMAT0000230 (miRBase mature sequence) | |
miR-199b | Rna | MIMAT0000672 (miRBase mature sequence) | |
miR-221 | Rna | MIMAT0017060 (miRBase mature sequence) | |
miR-222 | Rna | MIMAT0017061 (miRBase mature sequence) | |
miR-296 | Rna | MIMAT0000374 (miRBase mature sequence) | |
miR-29b | Rna | MIMAT0004523 (miRBase mature sequence) | |
miR-329 | Rna | MIMAT0017032 (miRBase mature sequence) | |
miR-342 | Rna | MIMAT0000590 (miRBase mature sequence) | |
miR-382 | Rna | MIMAT0004691 (miRBase mature sequence) | |
miR-409 | Rna | MIMAT0001090 (miRBase mature sequence) | |
miR-92 | Rna | MIMAT0000539 (miRBase mature sequence) |
Annotated Interactions
No annotated interactions