Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 20, 2025
The
majority
of
the
mouse
genome
is
composed
non-coding
regions,
which
harbor
numerous
regulatory
sequences
essential
for
gene
regulation.
While
extensive
research
focuses
on
enhancers
that
activate
expression,
role
silencers
repress
expression
remains
less
explored.
In
this
study,
first
genome-wide
identification
in
conducted.
embryonic
fibroblasts
(MEFs)
and
stem
cells
(mESCs),
89
596
115
165
are
identified,
respectively.
These
ubiquitously
distributed
across
predominantly
associated
with
low-expression
genes.
Additionally,
these
mainly
cell-specific
function
by
binding
to
repressive
transcription
factors
(TFs).
Further,
notably
enriched
histone
modification
H3K9me3.
It
observed
transformation
between
dual-function
correlated
intracellular
factor
concentrations,
accompanied
changes
epigenetic
modifications.
terms
biological
effects,
we
have
identified
can
enhance
induction
efficiency
MEFs
influence
pluripotency
mESCs.
Collectively,
work
offers
comprehensive
silencer
landscape
provides
strong
evidence
induced
pluripotent
(iPSCs).
Cell stem cell,
Год журнала:
2023,
Номер
30(12), С. 1569 - 1584
Опубликована: Окт. 18, 2023
Studies
of
mammalian
development
have
advanced
our
understanding
the
genetic,
epigenetic,
and
cellular
processes
that
orchestrate
embryogenesis
uncovered
new
insights
into
unique
aspects
human
embryogenesis.
Recent
studies
now
produced
first
epigenetic
maps
early
embryogenesis,
stimulating
ideas
about
reprogramming,
cell
fate
control,
potential
mechanisms
underpinning
developmental
plasticity
in
embryos.
In
this
review,
we
discuss
these
regulation
importance
for
safeguarding
development.
We
also
highlight
unanswered
questions
key
challenges
remain
to
be
addressed.
Substantial
epigenetic
resetting
during
early
embryo
development
from
fertilization
to
blastocyst
formation
ensures
zygotic
genome
activation
and
leads
progressive
cellular
heterogeneities1–3.
Mapping
single-cell
epigenomic
profiles
of
core
histone
modifications
that
cover
each
individual
cell
is
a
fundamental
goal
in
developmental
biology.
Here
we
develop
target
chromatin
indexing
tagmentation
(TACIT),
method
enabled
genome-coverage
profiling
seven
across
mouse
embryos.
We
integrated
these
with
RNA
sequencing
data
chart
resolution
landscape.
Multimodal
chromatin-state
annotations
showed
the
onset
at
two-cell
stage
already
primes
heterogeneities
totipotency.
used
machine
learning
identify
totipotency
gene
regulatory
networks,
including
stage-specific
transposable
elements
putative
transcription
factors.
CRISPR
combination
identified
factors
induced
embryonic
stem
cells.
Together
co-profiles
multiple
modifications,
developed
model
predicts
earliest
branching
towards
inner
mass
trophectoderm
latent
multimodal
space
identifies
previously
unknown
lineage-specifying
Our
work
provides
insights
into
reprogramming,
regulation
lineages
cell-fate
priming
pre-implantation
development.
Two
new
methods,
(TACIT)
combined
TACIT
(CoTACIT),
epigenome
lineage
tracing
zygotes
blastocysts.
Enhancers
are
cis-regulatory
elements
that
can
stimulate
gene
expression
from
distance,
and
drive
precise
spatiotemporal
profiles
during
development.
Functional
enhancers
display
specific
features
including
an
open
chromatin
conformation,
Histone
H3
lysine
27
acetylation,
4
mono-methylation
enrichment,
enhancer
RNAs
production.
These
modified
upon
developmental
cues
which
impacts
their
activity.
In
this
review,
we
describe
the
current
state
of
knowledge
about
functions
diverse
signatures
found
on
enhancers.
We
also
discuss
dynamic
changes
signatures,
impact
lineage
profiles,
development
or
cellular
differentiation.
Cell Reports,
Год журнала:
2023,
Номер
42(4), С. 112379 - 112379
Опубликована: Апрель 1, 2023
Over
the
past
few
decades,
many
attempts
have
been
made
to
capture
different
states
of
pluripotency
in
vitro.
Naive
and
primed
pluripotent
stem
cells,
corresponding
pre-
post-implantation
epiblasts,
respectively,
well
characterized
mice
can
be
interconverted
Here,
we
summarize
recently
reported
strategies
generate
human
naive
cells
We
discuss
their
applications
studies
regulatory
mechanisms
involved
early
developmental
processes,
including
identification
molecular
features,
X
chromosome
inactivation
modeling,
transposable
elements
regulation,
metabolic
characteristics,
cell
fate
as
potential
for
extraembryonic
differentiation
blastoid
construction
embryogenesis
modeling.
further
pluripotency-related
research,
8C-like
establishment
disease
also
highlight
limitations
current
studies,
such
imperfect
culture
conditions
inadequate
responsiveness
signals.
Clinical Epigenetics,
Год журнала:
2024,
Номер
16(1)
Опубликована: Окт. 17, 2024
Epigenetic
modifications
control
gene
expression
and
are
essential
for
turning
genes
on
off
to
regulate
maintain
differentiated
cell
types.
Epigenetics
also
modified
by
a
multitude
of
environmental
exposures,
including
diet
pollutants,
allowing
an
individual's
environment
influence
resultant
phenotypes
clinical
outcomes.
These
epigenetic
due
gene-environment
interactions
can
be
transmitted
across
generations,
raising
the
possibility
that
influences
occurred
in
one
generation
may
beyond
second
generation,
exerting
long-lasting
effect.
In
this
review,
we
cover
known
mechanisms
modification
acquisition,
reprogramming
persistence,
animal
models
human
studies
used
understand
multigenerational
transmission,
examples
environmentally
induced
change
its
transmission
generations.
We
highlight
importance
health
not
only
current
population
but
future
generations
will
experience
outcomes
through
inheritance.
EMBO Reports,
Год журнала:
2024,
Номер
25(4), С. 1721 - 1733
Опубликована: Март 25, 2024
Abstract
Remnants
of
transposable
elements
(TEs)
are
widely
expressed
throughout
mammalian
embryo
development.
Originally
infesting
our
genomes
as
selfish
and
acting
a
source
genome
instability,
several
these
have
been
co-opted
part
complex
system
regulation.
Many
TEs
lost
transposition
ability
their
transcriptional
potential
has
tampered
result
interactions
with
the
host
evolutionary
time.
It
proposed
that
ultimately
repurposed
to
function
gene
regulatory
hubs
scattered
genomes.
In
early
in
particular,
find
perfect
environment
naïve
chromatin
escape
repression
by
host.
As
consequence,
it
is
thought
hosts
found
ways
co-opt
TE
sequences
regulate
large-scale
changes
transcription
state
this
review,
we
discuss
examples
during
development,
for
co-option
regulation
pressures
on
