Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor

Zhousheng Xiao, R. Thomas, T. K. Hinson, Leigh Quarles

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5' end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon -1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA containing the unique Osf2 5' sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalGene
Volume214
Issue number1-2
DOIs
StatePublished - Jul 3 1998

Fingerprint

Core Binding Factor Alpha 1 Subunit
Exons
Protein Isoforms
Complementary DNA
RNA Splice Sites
Osteoblasts
Genes
Reading Frames
Terminator Codon
Transcription Initiation Site
Transcriptional Activation
Uncertainty
Transcription Factors
Nucleotides
Amino Acids
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor. / Xiao, Zhousheng; Thomas, R.; Hinson, T. K.; Quarles, Leigh.

In: Gene, Vol. 214, No. 1-2, 03.07.1998, p. 187-197.

Research output: Contribution to journalArticle

@article{4763a7c0405343589bd5e23cde47be2d,
title = "Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor",
abstract = "Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5' end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon -1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA containing the unique Osf2 5' sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.",
author = "Zhousheng Xiao and R. Thomas and Hinson, {T. K.} and Leigh Quarles",
year = "1998",
month = "7",
day = "3",
doi = "10.1016/S0378-1119(98)00227-3",
language = "English (US)",
volume = "214",
pages = "187--197",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor

AU - Xiao, Zhousheng

AU - Thomas, R.

AU - Hinson, T. K.

AU - Quarles, Leigh

PY - 1998/7/3

Y1 - 1998/7/3

N2 - Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5' end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon -1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA containing the unique Osf2 5' sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.

AB - Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5' end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon -1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA containing the unique Osf2 5' sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.

UR - http://www.scopus.com/inward/record.url?scp=0032479379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032479379&partnerID=8YFLogxK

U2 - 10.1016/S0378-1119(98)00227-3

DO - 10.1016/S0378-1119(98)00227-3

M3 - Article

VL - 214

SP - 187

EP - 197

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1-2

ER -