Molecular characterization of cbfβ 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

Research output: Contribution to journalArticle

105 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume567
DOIs
Publication statusPublished - 1 Feb 2015

Fingerprint

Transcription
Genes
Exons
Zebrafish
Proteins
Protein Isoforms
Transcription Factors
Functional analysis
DNA
Bone
Bone and Bones

Keywords

  • Alternative splicing
  • cbfβ
  • Functional analysis
  • Runx2
  • Transcription factor
  • Zebrafish

Cite this

Molecular characterization of cbfβ gene and identification of new transcription variants : Implications for function. / Simões, B.; Conceição, N.; Matias, A. C.; Bragança, J.; Kelsh, R. N.; Cancela, M. L.

In: Archives of Biochemistry and Biophysics, Vol. 567, 01.02.2015, p. 1-12.

Research output: Contribution to journalArticle

Simões, B. ; Conceição, N. ; Matias, A. C. ; Bragança, J. ; Kelsh, R. N. ; Cancela, M. L. / Molecular characterization of cbfβ gene and identification of new transcription variants : Implications for function. In: Archives of Biochemistry and Biophysics. 2015 ; Vol. 567. pp. 1-12.
@article{d3e750143cc9450190b94122c0fd003f,
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.",
keywords = "Alternative splicing, cbfβ, Functional analysis, Runx2, Transcription factor, Zebrafish",
author = "B. Sim{\~o}es and N. Concei{\cc}{\~a}o and Matias, {A. C.} and J. Bragan{\cc}a and Kelsh, {R. N.} and Cancela, {M. L.}",
year = "2015",
month = "2",
day = "1",
doi = "10.1016/j.abb.2014.12.023",
language = "English",
volume = "567",
pages = "1--12",
journal = "Archives of Biochemistry and Biophysics",
issn = "1096-0384",
publisher = "Elsevier Academic Press Inc",

}

TY - JOUR

T1 - Molecular characterization of cbfβ gene and identification of new transcription variants

T2 - Implications for function

AU - Simões, B.

AU - Conceição, N.

AU - Matias, A. C.

AU - Bragança, J.

AU - Kelsh, R. N.

AU - Cancela, M. L.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Alternative splicing

KW - cbfβ

KW - Functional analysis

KW - Runx2

KW - Transcription factor

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=84921028563&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1016/j.abb.2014.12.023

U2 - 10.1016/j.abb.2014.12.023

DO - 10.1016/j.abb.2014.12.023

M3 - Article

VL - 567

SP - 1

EP - 12

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 1096-0384

ER -