Abstract
Background
Genomic
imprinting
affects
gene
expression
in
a
parent-of-origin
manner
and
has
profound
impact
on
complex
traits
including
growth
behavior.
While
the
rat
is
widely
used
to
model
human
pathophysiology,
few
imprinted
genes
have
been
identified
this
murid.
To
systematically
identify
genomic
imprints
rat,
we
use
low
input
methods
for
genome-wide
analyses
of
DNA
methylation
profile
embryonic
extraembryonic
tissues
at
allele-specific
resolution.
Results
We
14
26
these
tissues,
respectively,
with
10
both
tissues.
Comparative
mouse
reveal
that
orthologous
associated
canonical
are
conserved
embryo
proper
Muridae
family.
However,
only
3
paternally
expressed
tissue
murids,
all
which
non-canonical
H3K27me3
imprints.
The
discovery
8
novel
unique
consistent
more
rapid
evolution
imprinting.
Meta-analysis
reveals
multiple
mechanisms
by
species-specific
may
be
established,
deposition
oocyte,
appearance
ZFP57
binding
motifs,
insertion
endogenous
retroviral
promoters.
Conclusions
In
summary,
provide
an
expanded
list
loci
extent
conservation
expression,
potential
responsible
Polycomb
repressive
complexes
1
and
2
(PRC1
PRC2)
cooperate
to
determine
cell
identity
by
epigenetic
gene
expression
regulation.
However,
the
mechanism
of
PRC2
recruitment
means
recognition
PRC1-mediated
H2AK119ub1
remains
poorly
understood.
Our
cryo-electron
microscopy
structure
with
cofactors
JARID2
AEBP2
bound
a
H2AK119ub1-containing
nucleosome
reveals
bridge
helix
in
EZH2
that
connects
SET
domain,
H3
tail,
nucleosomal
DNA.
each
interact
one
ubiquitin
H2A-H2B
surface.
stimulates
through
interactions
both
polycomb
protein
EED
H2AK119-ubiquitin,
whereas
has
an
additional
scaffolding
role.
The
presence
these
partially
overcomes
inhibitory
effect
H3K4me3
H3K36me3
exert
on
core
(in
absence
cofactors).
results
support
key
role
for
cross-talk
between
histone
modifications
activity.
Nature Genetics,
Год журнала:
2023,
Номер
55(9), С. 1567 - 1578
Опубликована: Сен. 1, 2023
Modified
parental
histones
are
segregated
symmetrically
to
daughter
DNA
strands
during
replication
and
can
be
inherited
through
mitosis.
How
this
may
sustain
the
epigenome
cell
identity
remains
unknown.
Here
we
show
that
transmission
of
histone-based
information
maintains
fidelity
embryonic
stem
plasticity.
Asymmetric
segregation
H3-H4
in
MCM2-2A
mutants
compromised
mitotic
inheritance
histone
modifications
globally
altered
epigenome.
This
included
widespread
spurious
deposition
repressive
modifications,
suggesting
elevated
epigenetic
noise.
Moreover,
H3K9me3
loss
at
repeats
caused
derepression
H3K27me3
redistribution
across
bivalent
promoters
correlated
with
misexpression
developmental
genes.
mutation
challenged
dynamic
transitions
cellular
states
cycle,
enhancing
naïve
pluripotency
reducing
lineage
priming
G1.
Furthermore,
competence
was
diminished,
correlating
impaired
exit
from
pluripotency.
Collectively,
argues
a
correctly
balanced
chromatin
landscape
able
support
mammalian
differentiation.
Science,
Год журнала:
2023,
Номер
381(6664), С. 1331 - 1337
Опубликована: Сен. 21, 2023
Polycomb
repressive
complex
2
(PRC2)
silences
genes
through
trimethylation
of
histone
H3K27.
PRC2
associates
with
numerous
precursor
messenger
RNAs
(pre-mRNAs)
and
long
noncoding
(lncRNAs)
a
binding
preference
for
G-quadruplex
RNA.
In
this
work,
we
present
3.3-Å-resolution
cryo–electron
microscopy
structure
bound
to
Notably,
RNA
mediates
the
dimerization
by
both
protomers
inducing
protein
interface
composed
two
copies
catalytic
subunit
EZH2,
thereby
blocking
nucleosome
DNA
interaction
H3
tail
accessibility.
Furthermore,
an
RNA-binding
loop
EZH2
facilitates
handoff
between
DNA,
another
activity
implicated
in
regulation
We
identified
gain-of-function
mutation
that
activates
zebrafish.
Our
results
reveal
mechanisms
RNA-mediated
chromatin-modifying
enzyme.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 7, 2025
Redox
signaling
acts
as
a
critical
mediator
in
the
dynamic
interactions
between
organisms
and
their
external
environment,
profoundly
influencing
both
onset
progression
of
various
diseases.
Under
physiological
conditions,
oxidative
free
radicals
generated
by
mitochondrial
respiratory
chain,
endoplasmic
reticulum,
NADPH
oxidases
can
be
effectively
neutralized
NRF2-mediated
antioxidant
responses.
These
responses
elevate
synthesis
superoxide
dismutase
(SOD),
catalase,
well
key
molecules
like
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
glutathione
(GSH),
thereby
maintaining
cellular
redox
homeostasis.
Disruption
this
finely
tuned
equilibrium
is
closely
linked
to
pathogenesis
wide
range
Recent
advances
have
broadened
our
understanding
molecular
mechanisms
underpinning
dysregulation,
highlighting
pivotal
roles
genomic
instability,
epigenetic
modifications,
protein
degradation,
metabolic
reprogramming.
findings
provide
foundation
for
exploring
regulation
mechanistic
basis
improving
therapeutic
strategies.
While
antioxidant-based
therapies
shown
early
promise
conditions
where
stress
plays
primary
pathological
role,
efficacy
diseases
characterized
complex,
multifactorial
etiologies
remains
controversial.
A
deeper,
context-specific
signaling,
particularly
redox-sensitive
proteins,
designing
targeted
aimed
at
re-establishing
balance.
Emerging
small
molecule
inhibitors
that
target
specific
cysteine
residues
proteins
demonstrated
promising
preclinical
outcomes,
setting
stage
forthcoming
clinical
trials.
In
review,
we
summarize
current
intricate
relationship
disease
also
discuss
how
these
insights
leveraged
optimize
strategies
practice.
Annual Review of Genomics and Human Genetics,
Год журнала:
2021,
Номер
22(1), С. 147 - 170
Опубликована: Март 30, 2021
Nucleosomes
wrap
DNA
and
impede
access
for
the
machinery
of
transcription.
The
core
histones
that
constitute
nucleosomes
are
subject
to
a
diversity
posttranslational
modifications,
or
marks,
impact
transcription
genes.
Their
functions
have
sometimes
been
difficult
infer
because
enzymes
write
read
them
complex,
multifunctional
proteins.
Here,
we
examine
evidence
marks
argue
major
perform
fairly
small
number
roles
in
either
promoting
preventing
it.
Acetylations
phosphorylations
on
histone
disrupt
histone–DNA
contacts
and/or
destabilize
promote
Ubiquitylations
stimulate
methylations
provide
scaffold
formation
silencing
complexes
resistance
those
complexes,
carry
memory
transcriptional
state.
Tail
deconstruct
particular
contexts.
We
speculate
these
simple
form
basis
regulation
by
marks.
Epigenetics & Chromatin,
Год журнала:
2022,
Номер
15(1)
Опубликована: Май 18, 2022
The
methylation
of
histone
H3
at
lysine
36
(H3K36me)
is
essential
for
maintaining
genomic
stability.
Indeed,
this
mark
proper
transcription,
recombination,
and
DNA
damage
response.
Loss-
gain-of-function
mutations
in
H3K36
methyltransferases
are
closely
linked
to
human
developmental
disorders
various
cancers.
Structural
analyses
suggest
that
nucleosomal
components
such
as
the
linker
a
hydrophobic
patch
constituted
by
H2A
likely
determinants
addition
tail,
which
encompasses
catalytic
SET
domain.
Interaction
with
nucleosome
collaborates
regulation
their
auto-inhibitory
changes
fine-tunes
precision
H3K36me
mediating
dimethylation
NSD2
NSD3
well
trimethylation
Set2/SETD2.
identification
specific
structural
features
cis-acting
factors
bind
different
forms
H3K36me,
particularly
di-(H3K36me2)
tri-(H3K36me3)
methylated
H3K36,
have
highlighted
intricacy
functional
significance.
Here,
we
consolidate
these
findings
offer
insight
H3K36me2
H3K36me3
conversion.
We
also
discuss
mechanisms
underlie
cooperation
between
other
chromatin
modifications
(in
particular,
H3K27me3,
acetylation,
N
