Characterization of a Mammalian Gene Related to the Yeast CCR4 General Transcription Factor and Revealed by Transposon Insertion

Murine intracisternal A-particles (IAPs) are reiterated retrovirus-like transposable elements that can act as insertional mutagens. Accordingly, we previously identified a chimeric transcript initiated at an IAP promoter and extending through a 3′-located open reading frame with significant similari...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-10, Vol.274 (43), p.31068-31075
Main Authors: Dupressoir, Anne, Barbot, Willy, Loireau, Marie-Paule, Heidmann, Thierry
Format: Article
Language:English
Subjects:
5' Untranslated Regions - genetics
Amino Acid Sequence
Animals
Base Sequence
CCR4 protein
DNA-Binding Proteins - genetics
Fungal Proteins - genetics
Genes, Intracisternal A-Particle
Humans
Mammals
mCCR4 gene
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Molecular Sequence Data
Mutagenesis, Insertional
Polymerase Chain Reaction
Promoter Regions, Genetic
Recombinant Fusion Proteins - biosynthesis
Ribonucleases
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins
Sequence Alignment
Sequence Homology, Amino Acid
Transcription Factors - genetics
Transcription, Genetic
Xenopus
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Summary:Murine intracisternal A-particles (IAPs) are reiterated retrovirus-like transposable elements that can act as insertional mutagens. Accordingly, we previously identified a chimeric transcript initiated at an IAP promoter and extending through a 3′-located open reading frame with significant similarity to the C-terminal domain of the yeast CCR4 general transcription factor. In this report, we characterize the corresponding murine gene, mCCR4, and its human homologue, thus providing the first description of CCR4-like factors in mammals. cDNA cloning revealed two mCCR4mRNAs of 2.7 and 3.1 kilobases, differing by their transcription start sites within the native mCCR4gene promoter, and encoding a putative 430-amino acid protein. The mCCR4gene contains three exons and two introns spanning almost 27 kilobases. The IAP insertion, detected only in some laboratory mouse strains, is recent and lies within the first intron. The 5′-region of the gene has features of housekeeping gene promoters. It lacks a TATA box but contains a CpG island and Sp1 sites. This region discloses strong promoter activity in transient transfection assays and also stimulates transcription in the reverse orientation, a feature common to other CpG island-containing promoters. Transcripts were detected in all the organs tested, although at a variable level, and displayed no strain-dependent differences relative to the IAP insertion, suggesting the existence of mechanisms preserving mCCR4transcription from the usually deleterious effects of intronic transposition. The strong amino acid conservation between the human, murine, and the previously identified XenopusCCR4-like proteins, is consistent with an important and conserved role for this protein in vertebrates.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.43.31068