296
Anthology of Human Repetitive DNA
directly related to the host cell. They can
affect host replication, imprinting, gene
silencing, transcriptional and posttran-
scriptional regulation, alternative splicing,
and evolution of genes and proteins. Below
are critically reviewed examples of such
involvements.
It
is
believed
that
alpha
satellites
are functional elements in human cen-
tromeres, and they bind key proteins in-
volved in host replication (see Sect. 2.2.1).
However, the complete lack of alpha
satellites in
de novo
-created (functional)
neocentromeres indicates that they may
represent well-adapted selFsh DNA.
It has been proposed that L1s may
be involved in inactivating chromosome
X in female somatic cells. This view is
based on the observed overrepresentation
of L1 elements on human chromosome X,
particularly near the X inactivation center.
However, the lack of L1 clusters in the
mouse X inactivation center indicates that
L1 accumulation near the inactivation start
may not be functionally related to the
imprinting of the X chromosome.
As mentioned in Sect. 3, TEs contain
different
transcription
regulation
sites
including
promoters,
enhancers,
and
polyadenylation
signals.
Accordingly,
insertions of TEs into regulatory regions
may alter the gene expression, and thus
they
can
be
negatively
selected.
±or
example, the majority of L1 and HERV
elements present in introns are in the
opposite orientation to the transcription
direction of the corresponding genes.
The
most
likely
explanation
is
that
polyA signals of these retrotransposons
prematurely terminate the transcription
if
inserted
in
the
direct
orientation.
Nevertheless, at least some TE-derived
polyA signals may be recruited by cellular
genes. Pol II transcription signals encoded
by endogenous retroviruses and DNA
transposons may serve as mobile ‘‘ready-
to-use’’ blocks involved in the evolution
of host genes. In several cases, TE-derived
promoters and enhancers are incorporated
into human genes. However, repetitive
elements are found in many genomic
regions, including promoters. Therefore,
repeats present in these regions may be
tolerated rather than being functional.
Potentially
important
regulation
of
genes by TEs may also occur at the RNA
level. Antisense transcripts from promoter
regions of TE inserted into introns can
inhibit gene expression. ±or instance, a
HERV-K element inserted into intron 9 of
complement C4 gene in the orientation op-
posite to the gene transcription produces
an antisense mRNA modulating the gene
expression. Transposable elements are fre-
quently found in untranslated regions of
many mRNAs. Therefore, these mRNAs
can also be regulated by transcripts derived
from other similar copies of genomic TEs.
Expressed SINE sequences can be acquired
by the host as novel RNA genes. Indeed,
BC200
, a small RNA gene expressed in
the primate brain, is the best-studied ex-
ample of an Alu element recruited by
the genome.
Protein-coding TEs can also be recruited
as host protein-coding genes. Table 11 lists
examples of TE-derived genes present in
the human genome. Well-known exam-
ples of such genes are V(D)J recombinase
and syncytin. V(D)J recombinase, which
catalyzes rearrangements of immunoglob-
ulin and T-cell receptor genes in lym-
phocytes, shares enzymatic characteristics
with mariner/Tc1-like DNA transposases.
Syncytin, a cell-fusion protein probably
participating in placental morphogenesis
and antiviral defense, was derived from
the
env
gene encoded by the HERV17
(HERV-W) retrovirus. While the V(D)J
previous page 296 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 298 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off