The Kelsh Lab

Robert Kelsh Lab's Fishy Business

Recent Paper

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📥  Papers

Recent paper published in Archives of Biochemistry and Biophysics (Jan 2015) doi: 10.1016/j.abb.2014.12.023.

Molecular characterization of cbfb gene and identification of new transcription variants: Implications for function

B. Simões, N. Conceição, A.C. Matias, J. Bragança, R.N. Kelsh, M.L. Cancela

 

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 master-regulator of bone-related gene transcription that contains a conserved DNA-binding domain (Runt 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 transcripts of the zebrafish cbfβ gene, one resulting in the known Cbfβ protein (with 187 amino-acids (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 (and resulting in a protein with 188 aa). Functional analysis of these isoforms provides insight into their role in regulating gene transcription. From the other seven variants two correspond to  premature early termination of Cbfβ forms, while the others show in-frame exon-skipping causing changes in the Cbfβ domain that may affect its function.