Microarray analysis reveals global modulation of endogenous retroelement transcription by microbes.

BACKGROUND:

A substantial proportion of both the mouse and human genomes comprise of endogenous retroelements (REs), which include endogenous retroviruses. Over evolutionary time, REs
accumulate inactivating mutations or deletions and thus lose the ability
to replicate. Additionally, REs can be transcriptionally repressed by
dedicated mechanisms of the host. Nevertheless, many of them still
possess and express intact open reading frames, and their
transcriptional activity has been associated with many physiological and
pathological processes of the host. However, this association remains
tenuous due to incomplete understanding of the mechanism by which RE
transcription is regulated. Here, we use a bioinformatics tool to
examine RE transcriptional activity, measured by microarrays, in murine
and human immune cells responding to microbial stimulation.

RESULTS:

Immune cell activation by microbial signals in vitro caused extensive changes
in the transcription not only of the host genes involved in the immune
response, but also of numerous REs. Modulated REs were frequently found
near or embedded within similarly-modulated host genes. Focusing on
probes reporting single-integration, intergenic REs, revealed extensive
transcriptional responsiveness of these elements to microbial signals.
Microbial stimulation modulated RE expression in a cell-intrinsic
manner. In line with these results, the transcriptional activity of
numerous REs followed characteristics in different tissues according to
exposure to environmental microbes and was further heavily altered
during viral infection or imbalances with intestinal microbiota, both in
mice and humans.

CONCLUSIONS:

Together, these results highlight the utility of improved methodologies in assessing RE
transcription profiles in both archived and new microarray data sets.
More importantly, application of this methodology suggests that immune
activation, as a result of infection with pathogens or dysbiosis with
commensal microbes, causes global modulation of RE transcription. RE
responsiveness to external stimuli should, therefore, be considered in
any association between RE transcription and disease.