Murine endogenous retroviruses and their transcriptional
Dewey D.Y. Ryu,
David G. Greenhalgh,
Biochemistry and Molecular Biology Graduate Group, University of California at Davis, Davis, California 95616, USA
Department of Chemical Engineering and Material Sciences, University of California at Davis, Davis, California 95616, USA
Department of Surgery, University of California at Davis, Sacramento, California 95817, USA
Shriners Hospitals for Children Northern California, Sacramento, California 95817, USA
Received: 19 April 2004 / Accepted: 13 July 2004
Viral transcripts from endogenous retroviruses
(ERVs) have been detected from patients with mul-
tiple sclerosis, breast cancer, leukemia, and schizo-
phrenia (Karlsson et al. 2001; Depil et al. 2002; Portis
2002; Wang-Johanning et al. 2003). While it is un-
known whether the presence of the viral transcripts
implicates ERVs in the pathological response, ERVs
contain the necessary elements for regulating
expression of host genes surrounding proviral inte-
gration sites (Majors 1990). With approximately 10%
of the mouse genome and 8% of the human genome
containing retrovirus-like elements, it is likely that
some of these elements may participate in control-
ling gene expression in normal and stress conditions
(Lander et al. 2001; Waterston et al. 2002).
While ERVs within the human genome are
inactive, there are transcription regulatory elements
and coding sequences of viral genes within the ret-
roviral sequences that are still intact (Schon et al.
2001). ERVs can affect gene expression in three ways:
(1) Insertion of an ERV can result in a gene inter-
ruption (Lower 1999), (2), intronic insertion of the
ERV can produce alternative splicing (Hatada et al.
2003), and (3) viral promoter, silencer, and enhancer
regions within the U3 region of the long terminal
repeat (LTR) can affect transcription in neighboring
genes (Ting et al. 1992; Dunn et al. 2003). The two
flanking LTRs of the ERV contain U3 sequences
comprising the majority of the viral transcriptional
regulatory elements. These cis-regulatory elements
can be tissue-specific and act synergistically with
neighboring promoters controlling transcription of
genes like b1,3-galactosyltransferase (Dunn et al.
2003). Certain viral promoters may be activated in
only specific tissues which include the colon and
salivary glands (Ting et al. 1992; Dunn et al. 2003).
While the presence of an alternative intronic pro-
moter can enhance transcription, aberrant splicing
due to ERV insertion can lead to the downregulation
of gene expression (Hughes 2001; Hatada et al. 2003).
Our recent findings that burn injury differentially
regulates the expression of murine endogenous ret-
roviruses (MuERVs) in a tissue-specific manner
suggests MuERVs’ involvement in the pathologic
processes in the host (Cho et al. 2002, 2003).
With endogenous retroviral research focusing on
human and porcine models, the profile of MuERVs
in the mouse genome has not been fully elucidated.
Previously, linkage mapping identified 57 noneco-
tropic MuERVs within the C57BL/6J strain of mice
(Frankel et al. 1989a,b, 1990). Further comprehensive
identification and characterization of transcription-
ally active MuERVs may contribute to better
understanding of their roles in injury/stress-medi-
ated gene regulation. In this study, 50 MuERVs were
identified by scanning the mouse genome using
PCR-amplified nonecotropic U3 probes and their
transcriptional potentials were analyzed.
The nucleotide sequence data reported in this paper have been
submitted to GenBank and have been assigned the accession
numbers: AY608536 (UA3), AY608537 (UA5), AY608538 (UA6),
AY608539 (UA7), AY608540 (UA8), AY608541 (UA9), AY608542
(UA10), AY608543 (UA11), AY608544 (UA12), AY608545 (UA13),
AY608546 (UA14), AY608547 (UA15), AY608548 (UA17),
AY608549 (UA18), AY608550 (UA19), AY608551 (UA20),
AY608552 (UA21), AY608553 (UA22), AY608554 (UA23),
AY608555 (UA24), AY608556 (UA25), AY608557 (UA26),
AY608558 (UA27), AY608559 (UA28), AY608560 (UA29),
AY608560 (UA30), AY608562 (UA31), AY608563 (UA32),
AY608564 (UA33), AY608565 (UA34), AY608566 (UA35),
AY608567 (UA36), AY608568 (UA37), AY608569 (UA38),
AY608570 (UA39), AY608571 (UA40), AY608572 (UA41),
AY608573 (UA42), AY608574 (UA43), AY608575 (UA44).
Correspondence to: Kiho Cho, E-mail: firstname.lastname@example.org
DOI: 10.1007/s00335-004-2409-x Volume 15, 914–923 (2004) Springer Science+Business Media, Inc. 2004