RRC ID 1719
Author Hikima J, Cioffi CC, Middleton DL, Wilson MR, Miller NW, Clem LW, Warr GW.
Title Evolution of transcriptional control of the IgH locus: characterization, expression, and function of TF12/HEB homologs of the catfish.
Journal J. Immunol.
Abstract The transcriptional enhancer (Emu3') of the IgH locus of the channel catfish, Ictalurus punctatus, differs from enhancers of the mammalian IgH locus in terms of its position, structure, and function. Transcription factors binding to multiple octamer motifs and a single muE5 motif (an E-box site, consensus CANNTG) interact for its function. E-box binding transcription factors of the class I basic helix-loop-helix family were cloned from a catfish B cell cDNA library in this study, and homologs of TF12/HEB were identified as the most highly represented E-proteins. Two alternatively spliced forms of catfish TF12 (termed CFEB1 and -2) were identified and contained regions homologous to the basic helix-loop-helix and activation domains of other vertebrate E-proteins. CFEB message is widely expressed, with CFEB1 message predominating over that of CFEB2. Both CFEB1 and -2 strongly activated transcription from a muE5-dependent artificial promoter. In catfish B cells, CFEB1 and -2 also activated transcription from the core region of the catfish IgH enhancer (Emu3') in a manner dependent on the presence of the muE5 site. Both CFEB1 and -2 bound the muE5 motif, and formed both homo- and heterodimers. CFEB1 and -2 were weakly active or inactive (in a promoter-dependent fashion) in mammalian B-lineage cells. Although E-proteins have been highly conserved in vertebrate evolution, the present results indicate that, at the phylogenetic level of a teleost fish, the TF12/HEB homolog differs from that of mammals in terms of 1) its high level of expression and 2) the presence of isoforms generated by alternative RNA processing.
Volume 173(9)
Pages 5476-84
Published 2004-11-1
PII 173/9/5476
PMID 15494495
MeSH Alternative Splicing Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors Binding Sites / genetics Cell Line Cell Line, Transformed Cloning, Molecular DNA-Binding Proteins / chemistry* DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism DNA-Binding Proteins / physiology Enhancer Elements, Genetic Evolution, Molecular* Genetic Markers / immunology Helix-Loop-Helix Motifs Ictaluridae / genetics Ictaluridae / immunology* Immunoglobulin Heavy Chains / genetics* Immunoglobulin Heavy Chains / metabolism* Immunoglobulin mu-Chains / genetics Immunoglobulin mu-Chains / metabolism Molecular Sequence Data Organ Specificity / genetics Organ Specificity / immunology Protein Isoforms / chemistry Protein Isoforms / genetics Protein Isoforms / metabolism Protein Isoforms / physiology RNA Precursors / biosynthesis RNA Precursors / metabolism RNA Processing, Post-Transcriptional Sequence Homology, Nucleic Acid* Transcription Factors / chemistry* Transcription Factors / genetics* Transcription Factors / metabolism Transcription Factors / physiology Transcription, Genetic* / immunology
IF 4.718
Times Cited 17