title: MEF2C orthologues from zebrafish: Evolution, expression and promoter regulation.
abstract: MEF2C is a crucial transcription factor for cranial neural crest cells development. An abnormal expression of this protein leads to severe abnormalities in craniofacial features. Recently, a human disease (MRD20) was described as a consequence of MEF2C haploinsufficiency. These patients show severe developmental delay, intellectual disability and dysmorphic features. Zebrafish presents two MEF2C orthologues, mef2ca and mef2cb. In this study we demonstrate a highly conserved pattern of chromosome localization for MEF2C between human and zebrafish, a similar protein sequence and tissue expression profile. We have focused our functional analysis on the zebrafish orthologue mef2cb. We identified three new exons through 5' RACE and described two new transcriptional start sites (TSS). These alternative TSS reflect the occurrence of two alternative promoters differentially regulated by nuclear factors related to craniofacial or neuronal development such as Sox9b, Sox10 and Runx2. We also predict that mef2cb gene may be post transcriptionally regulated by analysing the structure of its 5' UTR region, conserved throughout evolution. Our study provides new insights in MEF2C conservation and provides the first evidence of mef2cb regulation by both transcriptional and post transcriptional mechanisms, thus contributing to validate zebrafish as a good model for future studies concerning MEF2C dependent pathologies.
authors.affiliation: Centre of Marine Sciences/CCMAR, University of Algarve, Portugal; PhD Program in Biomedical Sciences, University of Algarve, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Adrião
authors.affiliation: Centre of Marine Sciences/CCMAR, University of Algarve, Portugal; Dept of Biomedical Sciences and Medicine, University of Algarve, Portugal. Electronic address: nconcei@ualg.pt.
authors.forename: Natércia
authors.initials: N
authors.lastname: Conceição
authors.affiliation: Centre of Marine Sciences/CCMAR, University of Algarve, Portugal; Dept of Biomedical Sciences and Medicine, University of Algarve, Portugal. Electronic address: lcancela@ualg.pt.
authors.forename: M Leonor
authors.initials: ML
authors.lastname: Cancela
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D064326:MEF2 Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*
chemical_list: D064326:MEF2 Transcription Factors
keywords: Post transcription; Promoter; Regulation; Zebrafish; mef2ca; mef2cb