title: Molecular characterization of cbfβ gene and identification of new transcription variants: implications for function.
abstract: The CBFβ gene encodes a transcription factor that, in combination with CBFα (also called Runx, runt-related transcription factor) regulates expression of several target genes. CBFβ interacts with all Runx family members, such as RUNX2, a regulator of bone-related gene transcription that contains a conserved DNA-binding domain. CBFβ stimulates DNA binding of the Runt domain, and is essential for most of the known functions of RUNX2. A comparative analysis of the zebrafish cbfβ gene and protein, and of its orthologous identified homologous proteins in different species indicates a highly conserved function. We cloned eleven zebrafish cbfβ gene transcripts, one resulting in the known Cbfβ protein (with 187 aa), and three additional variants resulting from skipping exon 5a (resulting in a protein with 174 aa) or exon 5b (resulting in a protein with 201 aa), both observed for the first time in zebrafish, and a completely novel isoform containing both exon 5a and 5b (resulting in a protein with 188 aa). Functional analysis of these isoforms provides insight into their role in regulating gene transcription. From the other variants two are premature termination Cbfβ forms, while the others show in-frame exon-skipping causing changes in the Cbfβ domain that may affect its function.
authors.affiliation: Department of Biomedical Sciences and Medicine/DCBM, University of Algarve, Faro, Portugal; PhD Program in Biomedical Sciences, University of Algarve, Faro, Portugal; Centre of Marine Sciences, University of Algarve, Faro, Portugal.
authors.forename: B
authors.initials: B
authors.lastname: Simões
authors.affiliation: Centre of Marine Sciences, University of Algarve, Faro, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Conceição
authors.affiliation: Department of Biomedical Sciences and Medicine/DCBM, University of Algarve, Faro, Portugal; Centre for Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Matias
authors.affiliation: Department of Biomedical Sciences and Medicine/DCBM, University of Algarve, Faro, Portugal; Centre for Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Bragança
authors.affiliation: Department of Biology and Biochemistry and Centre for Regenerative Medicine, University of Bath, Claverton Down, United Kingdom.
authors.forename: R N
authors.initials: RN
authors.lastname: Kelsh
authors.affiliation: Department of Biomedical Sciences and Medicine/DCBM, University of Algarve, Faro, Portugal; Centre of Marine Sciences, University of Algarve, Faro, Portugal. Electronic address: lcancela@ualg.pt.
authors.forename: M L
authors.initials: ML
authors.lastname: Cancela
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050658:Core Binding Factor beta Subunit; D020033:Protein Isoforms; D029961:Zebrafish Proteins
keywords: Alternative splicing; Functional analysis; Runx2; Transcription factor; Zebrafish; cbfβ