Publication Date:
2011-08-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashimoto, Satoru -- Boissel, Sarah -- Zarhrate, Mohammed -- Rio, Marlene -- Munnich, Arnold -- Egly, Jean-Marc -- Colleaux, Laurence -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1161-3. doi: 10.1126/science.1206638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite de Strasbourg, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21868677" target="_blank"〉PubMed〈/a〉
Keywords:
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
;
Cells, Cultured
;
Chromatin Immunoprecipitation
;
Early Growth Response Protein 1/genetics
;
Female
;
*Gene Expression Regulation
;
*Genes, Immediate-Early
;
Genes, fos
;
Genes, jun
;
Histones/metabolism
;
Humans
;
Intellectual Disability/*genetics
;
Male
;
Mediator Complex/*genetics
;
*Mutation, Missense
;
Pedigree
;
Promoter Regions, Genetic
;
Transcription Factors/metabolism
;
Transcriptional Activation
;
ets-Domain Protein Elk-1/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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