title: Transcriptional regulation of gilthead seabream bone morphogenetic protein (BMP) 2 gene by bone- and cartilage-related transcription factors.
abstract: Bone morphogenetic protein (BMP) 2 belongs to the transforming growth factor β (TGFβ) superfamily of cytokines and growth factors. While it plays important roles in embryo morphogenesis and organogenesis, BMP2 is also critical to bone and cartilage formation. Protein structure and function have been remarkably conserved throughout evolution and BMP2 transcription has been proposed to be tightly regulated, although few data is available. In this work we report the cloning and functional analysis of gilthead seabream BMP2 promoter. As in other vertebrates, seabream BMP2 gene has a 5′ non-coding exon, a feature already present in DPP gene, the fruit fly ortholog of vertebrate BMP2 gene, and maintained throughout evolution. In silico analysis of seabream BMP2 promoter revealed several binding sites for bone and cartilage related transcription factors (TFs) and their functionality was evaluated using promoter-luciferase constructions and TF-expressing vectors. Runt-related transcription factor 3 (RUNX3) was shown to negatively regulate BMP2 transcription and combination with the core binding factor β (CBFβ) further reduced transcriptional activity of the promoter. Although to a lesser extent, myocyte enhancer factor 2C (MEF2C) had also a negative effect on the regulation of BMP2 gene transcription, when associated with SRY (sex determining region Y)-box 9 (SOX9b). Finally, v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1) was able to slightly enhance BMP2 transcription. Data reported here provides new insights toward the better understanding of the transcriptional regulation of BMP2 gene in a bone and cartilage context.
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal; PhD Program in Biomedical Sciences, University of Algarve, Faro, Portugal; Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal.
authors.forename: Cátia L
authors.initials: CL
authors.lastname: Marques
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal; Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal.
authors.forename: M Leonor
authors.initials: ML
authors.lastname: Cancela
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal. Electronic address: vlaize@ualg.pt.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laizé
mesh_terms: D000818:Animals; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D001842:Bone and Bones / Q000502:physiology; D002356:Cartilage / Q000502:physiology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D021541:Sea Bream / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D055396:Bone Morphogenetic Protein 2; D050677:Core Binding Factor Alpha 3 Subunit; D050658:Core Binding Factor beta Subunit; D029941:Fish Proteins; D064326:MEF2 Transcription Factors; C588168:Mef2ca protein, zebrafish; D050784:Proto-Oncogene Protein c-ets-1; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins
keywords: Myocyte enhancer factor 2C (MEF2C); Promoter activity; Runt-related transcription factor 3 (RUNX3); SRY (sex determining region Y)-box 9b (SOX9b); Transcriptional regulation; v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1)