Biology Reference
In-Depth Information
cell types (Swergold, 1990; Yang
, 2003) and the reported variation in the
extent of L1 mRNA processing (Belancio
et al.
, 2010b) the exposure to the L1-
associated DNA damage is expected to vary in a tissue-specific manner. Along
with the significant broadening of the potential spectrum of L1-induced DNA
damage comes the importance of understanding of the time, location, and levels
of TE expression in human tissues making unraveling of the somatic L1 expres-
sion an important aspect of L1 biology.
et al.
C. Mechanisms controlling TE expression and activity
Even though many critical elements controlling TE expression and activity
remain unknown, a plethora of cellular mechanisms that control human TE
expression and activity has been unveiled to date. Based on the fact that TEs can
significantly perturb the normal function of the genome it is not surprising that
host organisms employed a multifaceted network of road blocks designed to
suppress TE expression and mobilization. Of the three currently active human
TEs, L1 expression and activity is the best studied to date, mostly due to the fact
that L1s are the driving force of any TE-related unrest in the human genome.
Among the well-characterized mechanisms influencing human TE expression
and activity are transcriptional regulation, promoter methylation, RNA proces-
sing, and cellular pathways involved in controlling TE-induced damage.
The number and diversity of the barriers erected by mammalian cells to suppress
TE expression speaks to the importance of keeping the production of these
elements in check.
One of the first levels of defense controlling TE expression is promoter
strength and availability of the transcription factors necessary to drive RNA
production. Members of the SOX and RUNX family of transcription factors as
well as steroid hormones can regulate L1 expression dictating tissue specificity of
L1 transcription (Morales
, 2003).
YY1 transcription factor does not change transcription efficiency, but it is
important for the proper site of transcription initiation at the L1 promoter
(Athanikar
et al.
, 2002; Tchenio
et al.
, 2000; Yang
et al.
, 2004). Genomic sequences immediately upstream of the L1
integration site can stimulate L1 promoter strength potentially rendering some
L1 loci the ability to contribute more molecules than others to the combined
pool of L1 transcripts (Lavie
et al.
, 2004). A similar situation is reported for Alu
elements; while transcription of Alu promoter alone by Pol-III is relatively weak
but upstream genomic sequences can stimulate it by several fold (Roy
et al.
,
2000). Expression of SVA elements is reported to be driven by cellular promoters
present upstream of the SVA integration sites suggesting that these elements are
likely to exhibit significant variation in their total expression, with different
SVA loci differentially contributing to the combined pool of SVA transcripts
(Damert
et al.
et al.
, 2009).
