Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders - PubMed (original) (raw)
Comparative Study
. 2004 Mar 15;13(6):629-39.
doi: 10.1093/hmg/ddh063. Epub 2004 Jan 20.
Affiliations
- PMID: 14734626
- DOI: 10.1093/hmg/ddh063
Comparative Study
Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders
Rodney C Samaco et al. Hum Mol Genet. 2004.
Abstract
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Although MECP2 is ubiquitously transcribed, MeCP2 expression is developmentally regulated and heterogeneous in neuronal subpopulations, defined as MeCP2(lo) and MeCP2(hi). To test the hypothesis that pathways affecting MeCP2 expression changes may be defective in RTT, autism and other neurodevelopmental disorders without MECP2 mutations, a high-throughput quantitation of MeCP2 expression was performed on a tissue microarray containing frontal cortex samples from 28 different patients with neurodevelopmental disorders and age-matched controls. Combined quantitative analyses of MeCP2 protein and alternatively polyadenylated transcript levels were performed by laser scanning cytometry and tested for significant differences from age-matched controls. Normal cerebral samples showed an increase in total MeCP2 expression and the percentage of MeCP2(hi) cells with age that could be explained by increased MECP2 transcription within the MeCP2(hi) population. A significant decrease in the relative usage of the long transcript in the MeCP2(lo) population was observed in postnatal compared to fetal brain, but alternate polyadenylation did not correlate with MeCP2 expression changes at the single cell level. Brain samples from several related neurodevelopmental disorders, including autism, pervasive developmental disorder, Prader-Willi and Angelman syndromes showed significant differences in MeCP2 expression from age-matched controls by apparently different transcriptional and post-transcriptional mechanisms. These results suggest that multiple pathways regulate the complex developmental expression of MeCP2 and are defective in autism-spectrum disorders in addition to RTT.
Similar articles
- Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3.
Samaco RC, Hogart A, LaSalle JM. Samaco RC, et al. Hum Mol Genet. 2005 Feb 15;14(4):483-92. doi: 10.1093/hmg/ddi045. Epub 2004 Dec 22. Hum Mol Genet. 2005. PMID: 15615769 Free PMC article. - Quantitative localization of heterogeneous methyl-CpG-binding protein 2 (MeCP2) expression phenotypes in normal and Rett syndrome brain by laser scanning cytometry.
LaSalle JM, Goldstine J, Balmer D, Greco CM. LaSalle JM, et al. Hum Mol Genet. 2001 Aug 15;10(17):1729-40. doi: 10.1093/hmg/10.17.1729. Hum Mol Genet. 2001. PMID: 11532982 - Homologous pairing of 15q11-13 imprinted domains in brain is developmentally regulated but deficient in Rett and autism samples.
Thatcher KN, Peddada S, Yasui DH, Lasalle JM. Thatcher KN, et al. Hum Mol Genet. 2005 Mar 15;14(6):785-97. doi: 10.1093/hmg/ddi073. Epub 2005 Feb 2. Hum Mol Genet. 2005. PMID: 15689352 - Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome.
Van den Veyver IB, Zoghbi HY. Van den Veyver IB, et al. Brain Dev. 2001 Dec;23 Suppl 1:S147-51. doi: 10.1016/s0387-7604(01)00376-x. Brain Dev. 2001. PMID: 11738862 Review. - Rett syndrome: of girls and mice--lessons for regression in autism.
Glaze DG. Glaze DG. Ment Retard Dev Disabil Res Rev. 2004;10(2):154-8. doi: 10.1002/mrdd.20030. Ment Retard Dev Disabil Res Rev. 2004. PMID: 15362175 Review.
Cited by
- A Spectrum of Solutions: Unveiling Non-Pharmacological Approaches to Manage Autism Spectrum Disorder.
Mondal A, Sharma R, Abiha U, Ahmad F, Karan A, Jayaraj RL, Sundar V. Mondal A, et al. Medicina (Kaunas). 2023 Aug 31;59(9):1584. doi: 10.3390/medicina59091584. Medicina (Kaunas). 2023. PMID: 37763703 Free PMC article. Review. - Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder: A Literature Review.
Carpita B, Migli L, Chiarantini I, Battaglini S, Montalbano C, Carmassi C, Cremone IM, Dell'Osso L. Carpita B, et al. Brain Sci. 2022 Jun 16;12(6):792. doi: 10.3390/brainsci12060792. Brain Sci. 2022. PMID: 35741677 Free PMC article. Review. - Dopaminergic Dysregulation in Syndromic Autism Spectrum Disorders: Insights From Genetic Mouse Models.
Kosillo P, Bateup HS. Kosillo P, et al. Front Neural Circuits. 2021 Jul 23;15:700968. doi: 10.3389/fncir.2021.700968. eCollection 2021. Front Neural Circuits. 2021. PMID: 34366796 Free PMC article. Review. - Regulation, diversity and function of MECP2 exon and 3'UTR isoforms.
Rodrigues DC, Mufteev M, Ellis J. Rodrigues DC, et al. Hum Mol Genet. 2020 Sep 30;29(R1):R89-R99. doi: 10.1093/hmg/ddaa154. Hum Mol Genet. 2020. PMID: 32681172 Free PMC article. Review. - Writers and Readers of DNA Methylation/Hydroxymethylation in Physiological Aging and Its Impact on Cognitive Function.
Torres RF, Kouro R, Kerr B. Torres RF, et al. Neural Plast. 2019 Jul 14;2019:5982625. doi: 10.1155/2019/5982625. eCollection 2019. Neural Plast. 2019. PMID: 31396272 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous