bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 25, 2024
Transposable
elements
(TEs)
provide
sequences
that
are
powerful
cis-regulatory
drivers
of
gene
expression
programmes.
This
is
particularly
apparent
during
early
development
when
many
TEs
become
de-repressed.
MERVL
highly
yet
transiently
upregulated
in
mouse
totipotent
2-cell
(2C)
embryos
major
zygotic
genome
activation
(ZGA),
and
2C-like
cells
vitro.
One
the
most
activators
pioneer
transcription
factor,
Dux.
However,
differences
lie
requirement
for
Dux
versus
embryos,
unclear
reasons.
Moreover,
sustained
causes
cell
toxicity
multiple
types,
which
may
or
not
be
linked
to
activation.
Using
a
CRISPR-activation,
2C-GFP
reporter
system,
we
have
unpicked
relative
role
ZGA,
totipotent-like
characteristics
toxicity.
We
find
direct
comprises
only
portion
Dux-dependent
transcriptome,
sufficient
expanded
fate
potential,
but
other
totipotency
features.
Conversely,
Dux-induced
pathology
independent
involves
induction
pro-apoptotic
Noxa.
Our
study
highlights
complexity
Dux-MERVL
transcriptional
network
uncovers
new
player
Dux-driven
pathology.
Cancer
cells
exhibit
rewired
transcriptional
regulatory
networks
that
promote
tumor
growth
and
survival.
However,
the
mechanisms
underlying
formation
of
these
pathological
remain
poorly
understood.
Through
a
pan-cancer
epigenomic
analysis,
we
found
primate-specific
endogenous
retroviruses
(ERVs)
are
rich
source
enhancers
displaying
cancer-specific
activity.
In
colorectal
cancer
other
epithelial
tumors,
oncogenic
MAPK/AP1
signaling
drives
activation
derived
from
ERV
family
LTR10.
Functional
studies
in
revealed
LTR10
elements
regulate
tumor-specific
expression
multiple
genes
associated
with
tumorigenesis,
such
as
ATG12
XRCC4
.
Within
human
population,
individual
germline
somatic
structural
variation
resulting
highly
mutable
internal
tandem
repeat
region,
which
affects
AP1
binding
Our
findings
reveal
ERV-derived
contribute
to
dysregulation
response
shape
evolution
networks.
Biomolecules,
Год журнала:
2024,
Номер
14(6), С. 720 - 720
Опубликована: Июнь 18, 2024
Zygotic
genome
activation
(ZGA)
is
a
pivotal
event
in
mammalian
embryogenesis,
marking
the
transition
from
maternal
to
zygotic
control
of
development.
During
ZGA
process
that
characterized
by
intricate
cascade
gene
expression,
who
tipped
first
domino
meticulously
arranged
sequence
subject
paramount
interest.
Recently,
Dux,
Obox
and
Nr5a2
were
identified
as
pioneer
transcription
factors
reside
at
top
transcriptional
hierarchy.
Through
co-option
retrotransposon
elements
hubs
for
activation,
these
rewire
regulatory
network,
thus
initiating
ZGA.
In
this
review,
we
provide
snapshot
mechanisms
underlying
functions
factors.
We
propose
starting
point
where
embryo’s
own
begins
influence
development
trajectory,
therefore
in-depth
dissecting
during
will
form
cornerstone
our
understanding
early
embryonic
development,
which
pave
way
advancing
grasp
developmental
biology
optimizing
vitro
production
(IVP)
techniques.
EMBO Reports,
Год журнала:
2024,
Номер
25(10), С. 4113 - 4130
Опубликована: Авг. 19, 2024
Zygotic
genome
activation
(ZGA),
the
first
transcription
event
following
fertilization,
kickstarts
embryonic
program
that
takes
over
control
of
early
development
from
maternal
products.
How
ZGA
occurs,
especially
in
mammals,
is
poorly
understood
due
to
limited
amount
research
materials.
With
rapid
single-cell
and
low-input
technologies,
remarkable
progress
made
past
decade
has
unveiled
dramatic
transitions
epigenomes,
transcriptomes,
proteomes,
metabolomes
associated
with
ZGA.
Moreover,
functional
investigations
are
yielding
insights
into
key
regulators
ZGA,
among
which
two
major
classes
players
emerging:
licensors
specifiers.
Licensors
would
permission
its
timing
during
Accumulating
evidence
suggests
such
include
apparatus
nuclear
gatekeepers.
Specifiers
instruct
specific
genes
These
specifiers
factors
present
at
this
stage,
often
facilitated
by
epigenetic
regulators.
Based
on
data
primarily
mammals
but
also
results
other
species,
we
discuss
review
how
recent
sheds
light
molecular
regulation
executors,
including
Molecular Medicine,
Год журнала:
2025,
Номер
31(1)
Опубликована: Март 12, 2025
Abstract
Transposable
elements
(TEs)
comprise
approximately
half
of
eukaryotic
genomes
and
significantly
contribute
to
genome
plasticity.
In
this
study,
we
focused
on
a
specific
TE,
MERVL,
which
exhibits
particular
expression
during
the
2-cell
stage
commonly
serves
as
an
indicator
embryonic
totipotency.
However,
its
precise
role
in
embryo
development
remains
mysterious.
We
utilized
DRUG-seq
investigate
effects
oxidative
damage
genes
TEs
expression.
Our
findings
revealed
that
exposure
hydrogen
peroxide
(H
2
O
)
could
induce
DNA
damage,
apoptosis,
incomplete
demethylation
embryos,
were
potentially
associated
with
MERVL
To
further
explore
function,
antisense
nucleotides
(ASO)
targeting
constructed
knockdown
early
embryos.
Notably,
led
occurrence
apoptosis
stage,
consequently
reducing
number
embryos
progress
blastocyst
stage.
Moreover,
discovered
exerted
influence
reprogramming
methylation.
MERVL-deficient
activity
demethylase
ten-eleven
translocation
3
(TET3)
was
suppressed,
resulting
impaired
when
compared
normal
development.
This
impairment
might
underpin
mechanism
impacts
Collectively,
our
study
not
only
verified
crucial
but
also
probed
regulatory
function
methylation
reprogramming,
thereby
laying
solid
foundation
for
investigations
into
MERVL's
role.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 18, 2024
Abstract
Circadian
oscillations
of
gene
transcripts
rely
on
a
negative
feedback
loop
executed
by
the
activating
BMAL1-CLOCK
heterodimer
and
its
regulators
PER
CRY.
Although
circadian
rhythms
CLOCK
protein
are
mostly
absent
during
embryogenesis,
lack
BMAL1
prenatal
development
causes
an
early
aging
phenotype
adulthood,
suggesting
that
carries
out
unknown
non-circadian
function
organism
is
fundamental
for
healthy
adult
life.
Here,
we
show
interacts
with
TRIM28
represses
transcription
totipotency-associated
MERVL
retrotransposons
in
mouse
pluripotent
cells.
Deletion
Bmal1
leads
to
genome-wide
upregulation
MERVLs,
changes
three-dimensional
organization
genome,
acquisition
features.
Overall,
demonstrate
cells
redeployed
as
transcriptional
repressor
transposable
elements
(TEs)
CLOCK-independent
way.
We
propose
BMAL1-TRIM28
activity
life
essential
optimal
health
span
mammals.
