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J Biol Chem, Vol. 274, Issue 43, 31068-31075, October 22, 1999
From the Unité des Rétrovirus Endogènes et
Eléments Rétroïdes des Eucaryotes Supérieurs,
CNRS UMR 1573, Institut Gustave Roussy, 39 rue Camille Desmoulins,
94805 Villejuif Cedex, France
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 mCCR4 mRNAs of 2.7 and 3.1 kilobases, differing by
their transcription start sites within the native mCCR4
gene promoter, and encoding a putative 430-amino acid protein.
The mCCR4 gene 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
mCCR4 transcription from the usually deleterious effects of
intronic transposition. The strong amino acid conservation between the
human, murine, and the previously identified Xenopus
CCR4-like proteins, is consistent with an important and conserved role
for this protein in vertebrates.
Characterization of a Mammalian Gene Related to the Yeast
CCR4 General Transcription Factor and Revealed by Transposon
Insertion
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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