Transcript Retrotransposons Regulate Host Genes in Mouse Oocytes and

Retrotransposons Regulate
Host Genes in Mouse
Oocytes and
Preimplantation Embryos
127th lab seminar
Ho-Su Shin
2004.11.6
Introductions
1.
TEs are significant component of eukaryotic
genomes, occupying more than one third of
mouse and human genome
2.
TEs can function as regulatory units for host
genes and appear to contribute to many
mammlian gene regulatory sequences
3.
The effect of TEs whthin their host genome can
be viewd as essentially neutral although…..
4.
TEs exert a powerful influence on genome
evolution
Fig.1. Mouse develpmental stages in oocyte&embryo
Fig.2. Distribution of 14,813 2-cell library ESTs among six broad categories
A.V. Evsikov., et al, 2004
So, they focus in detail on LTR class Ⅲ
retrotransposons, which include members
of the mammalian apparent LTR
retrotransposon(MaLR) and ERV-L
families, and investigate the ability of TEs
to act as stage specific alternative promoters
for a member of host genes
Fig. 3. Expression of mobile elements in mouse oocytes and
preimplantation embryo
A.V. Evsikov., et al, 2004
Results
1. LTR Class III Retrotransposons Are Preferentially
Expressed in Full-Grown Oocytes and Cleavage Stage
Embryos
Abbreviations
1.MT : mouse transcript non autonomous
retrotransposon
2.ORR1 : origin region repeat 1 nonautonomous
retrotranspospn
3.RLTR1B : subfamily of ERV1
4.IAPEz : intracisternal A – type particle provirus
ERV-K family
5.Mor : Morula
6.Bl : Blastocyst
LTR
classⅢ
LTR classⅠ
LTR classⅡ
2.Transposable Elements Provide an Alternative
5 Exon Transcripts in Full-Grown Oocytes and
Cleavage Stage Embryos
3. Origin of Chimeric Transcripts
Chimeric transcripts were missing all exons located upstream
of TEs and usually lacked one or more conventional 5’ exons
when the TE was located up stream of the gene locus
Chimeric transcripts were used to determine
(1)whether there was evidence that such transcripts were
splice isoforms, as opposed to transcripts arising from an
alternative promoter
(2) whether such transcripts could be found in other cDNA
libraries
4. Conserved LTR splice donor site with Gene
AT-rich splice acceptor site characterize MTA
LTR – derived chimeric transcript
(A) Aligned consensus MaLR LTRs
from RepBase compared with a
consensus mammalian splice
site
(B) Alignment of 10 MTAs that
contribute 5’ sequence to
chimeric transcripts.
(C) Orientation
bias of MaLR
elements within
introns.
(D) MTA LTRs
splice into
acceptor sites
with a high
upstream AT
content.
5. MT LTRs and developmental regulation of
Chimeric transcript expression
Investigation of MTderived chimeric
transcripts relative to
conventional nonchimeric
couterparts
They exhibited different
patterns of expression
4. MT-Derived SPIN protein in 2-cell stage
mouse embryo
The predicted N termini of the chimeric and conventional
SPIN protein isoforms have scripts might be regulated by
another promoter,weused different potential
phosphorylation sites suggesting that these two isoforms
may function genomic sequence differently.
5. Phylogenetic conservation
To approach the question of
functional significance from
expression MT LTR different
angle, class III LTR that
contribute to specific chimeric
transcripts were assessed for
their evolutionary
conservation.
Trophectoderm
(TE)
Inner cell
Mass( ICM)
blastocyst
Discussions
1.
2.
3.
4.
5.
Different LTR retrotransposons have specific
developmentally regulated expression patterns
TE-derived chimeric transcripts introduces
variation in gene expression and potentially
altered gene function either at the RNA or
protein level
TEs modify gene products and potentially
initiate new gene regulatory systems in oocyte
and early embryo
Oocyte, embryos, and the biology of MaLR
Mechanisms of differential TE expression in the
oocyte and preimplantation embryo
Concluding Remarks
Sequential activation and silencing of MaLR and
other retrotransposons in oocytes and
preimplantation embryos, together with the known
links between transposon silencing and chromatin
remodeling, lead us to propose that genome
remodeling during this period could be initiated and
ordered by retrotransposon expression.
Concurrent analysis of both transcriptional activaton
and epigenetic modifications of specific genomic loci
will be required to explore this idea.