MED23 mutation links intellectual disability to dysregulation of immediate early gene expression - PubMed (original) (raw)
. 2011 Aug 26;333(6046):1161-3.
doi: 10.1126/science.1206638.
Affiliations
- PMID: 21868677
- DOI: 10.1126/science.1206638
MED23 mutation links intellectual disability to dysregulation of immediate early gene expression
Satoru Hashimoto et al. Science. 2011.
Abstract
MED23 is a subunit of the Mediator complex, a key regulator of protein-coding gene expression. Here, we report a missense mutation (p. R617Q) in MED23 that cosegregates with nonsyndromic autosomal recessive intellectual disability. This mutation specifically impaired the response of JUN and FOS immediate early genes (IEGs) to serum mitogens by altering the interaction between enhancer-bound transcription factors (TCF4 and ELK1, respectively) and Mediator. Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurological disorders linked to mutations in other Mediator subunits or proteins interacting with MED. These findings highlight the crucial role of Mediator in brain development and functioning and suggest that altered IEG expression might be a common molecular hallmark of cognitive deficit.
Comment in
- Mutations in the Mediator subunit MED23 link intellectual disability to immediate early gene regulation.
Goh YS, Grants JM. Goh YS, et al. Clin Genet. 2012 May;81(5):430. doi: 10.1111/j.1399-0004.2011.01821.x. Epub 2011 Dec 30. Clin Genet. 2012. PMID: 22129135 No abstract available.
Similar articles
- An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities.
Yang Y, Li C, Chen Z, Zhang Y, Tian Q, Sun M, Zhang S, Yu M, Wang G. Yang Y, et al. Nucleic Acids Res. 2023 Mar 21;51(5):2137-2150. doi: 10.1093/nar/gkad025. Nucleic Acids Res. 2023. PMID: 36718943 Free PMC article. - Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome.
Forrest M, Chapman RM, Doyle AM, Tinsley CL, Waite A, Blake DJ. Forrest M, et al. Hum Mutat. 2012 Dec;33(12):1676-86. doi: 10.1002/humu.22160. Epub 2012 Jul 27. Hum Mutat. 2012. PMID: 22777675 - Mediator complex in neurological disease.
Schiano C, Luongo L, Maione S, Napoli C. Schiano C, et al. Life Sci. 2023 Sep 15;329:121986. doi: 10.1016/j.lfs.2023.121986. Epub 2023 Jul 28. Life Sci. 2023. PMID: 37516429 Review. - Increasing evidence of pathogenic role of the Mediator (MED) complex in the development of cardiovascular diseases.
Napoli C, Schiano C, Soricelli A. Napoli C, et al. Biochimie. 2019 Oct;165:1-8. doi: 10.1016/j.biochi.2019.06.014. Epub 2019 Jun 27. Biochimie. 2019. PMID: 31255603 Review.
Cited by
- MED23-associated intellectual disability in a non-consanguineous family.
Trehan A, Brady JM, Maduro V, Bone WP, Huang Y, Golas GA, Kane MS, Lee PR, Thurm A, Gropman AL, Paul SM, Vezina G, Markello TC, Gahl WA, Boerkoel CF, Tifft CJ. Trehan A, et al. Am J Med Genet A. 2015 Jun;167(6):1374-80. doi: 10.1002/ajmg.a.37047. Epub 2015 Apr 2. Am J Med Genet A. 2015. PMID: 25845469 Free PMC article. - De novo mutations in genes of mediator complex causing syndromic intellectual disability: mediatorpathy or transcriptomopathy?
Caro-Llopis A, Rosello M, Orellana C, Oltra S, Monfort S, Mayo S, Martinez F. Caro-Llopis A, et al. Pediatr Res. 2016 Dec;80(6):809-815. doi: 10.1038/pr.2016.162. Epub 2016 Aug 8. Pediatr Res. 2016. PMID: 27500536 - Exploring the Role of Enhancer-Mediated Transcriptional Regulation in Precision Biology.
Wang X, Liu D, Luo J, Kong D, Zhang Y. Wang X, et al. Int J Mol Sci. 2023 Jun 29;24(13):10843. doi: 10.3390/ijms241310843. Int J Mol Sci. 2023. PMID: 37446021 Free PMC article. Review. - The role of nuclear bodies in gene expression and disease.
Morimoto M, Boerkoel CF. Morimoto M, et al. Biology (Basel). 2013 Jul 9;2(3):976-1033. doi: 10.3390/biology2030976. Biology (Basel). 2013. PMID: 24040563 Free PMC article. - Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes.
Bomkamp C, Tripathy SJ, Bengtsson Gonzales C, Hjerling-Leffler J, Craig AM, Pavlidis P. Bomkamp C, et al. PLoS Comput Biol. 2019 Jun 18;15(6):e1007113. doi: 10.1371/journal.pcbi.1007113. eCollection 2019 Jun. PLoS Comput Biol. 2019. PMID: 31211786 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous