Abstract
Basal‐like
breast
cancer
(BLBC)
is
the
most
aggressive
molecular
subtype
of
with
worse
prognosis
and
fewer
treatment
options.
The
underlying
mechanisms
upon
BLBC
transcriptional
dysregulation
its
upstream
transcription
factors
(TFs)
remain
unclear.
Here,
among
hyperactive
candidate
TFs
identified
by
bioinformatic
analysis,
POU4F1
uniquely
upregulated
in
associated
poor
prognosis.
necessary
for
tumor
growth
malignant
phenotypes
through
regulating
G1/S
transition
direct
binding
at
promoter
CDK2
CCND1.
More
importantly,
maintains
identity
repressing
ERα
expression
CDK2‐mediated
EZH2
phosphorylation
subsequent
H3K27me3
modification
ESR1
promoter.
Knocking
out
cells
reactivates
functional
expression,
rendering
sensitive
to
tamoxifen
treatment.
In‐depth
epigenetic
analysis
reveals
that
subtype‐specific
re‐configuration
activation
bivalent
chromatin
contributes
unique
BLBC,
which
maintained
DNA
demethylase
TET1.
Together,
these
results
reveal
a
epigenetically
activated
TF
critical
role
promoting
maintaining
suggesting
potential
therapeutic
target
BLBC.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 18, 2024
Abstract
Tumorigenesis
is
a
multistep
process,
with
oncogenic
mutations
in
normal
cell
conferring
clonal
advantage
as
the
initial
event.
However,
despite
pervasive
somatic
and
expansion
tissues,
their
transformation
into
cancer
remains
rare
event,
indicating
presence
of
additional
driver
events
for
progression
to
an
irreversible,
highly
heterogeneous,
invasive
lesion.
Recently,
researchers
are
emphasizing
mechanisms
environmental
tumor
risk
factors
epigenetic
alterations
that
profoundly
influencing
early
malignant
evolution,
independently
inducing
mutations.
Additionally,
evolution
tumorigenesis
reflects
multifaceted
interplay
between
cell-intrinsic
identities
various
cell-extrinsic
exert
selective
pressures
either
restrain
uncontrolled
proliferation
or
allow
specific
clones
progress
tumors.
by
which
induce
both
intrinsic
cellular
competency
remodel
stress
facilitate
not
fully
understood.
In
this
review,
we
summarize
genetic,
epigenetic,
external
events,
effects
on
co-evolution
transformed
cells
ecosystem
during
initiation
evolution.
A
deeper
understanding
earliest
molecular
holds
promise
translational
applications,
predicting
individuals
at
high-risk
developing
strategies
intercept
transformation.
Trends in Cell Biology,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 1, 2024
Epigenetic
modifications,
including
posttranslational
modifications
of
histones,
are
closely
linked
to
transcriptional
regulation.
Trimethylated
H3
lysine
4
(H3K4me3)
is
one
the
most
studied
histone
owing
its
enrichment
at
start
sites
transcription
and
association
with
gene
expression
processes
determining
cell
fate,
development,
disease.
In
this
review,
we
focus
on
recent
studies
that
have
yielded
insights
into
how
levels
patterns
H3K4me3
regulated,
contributes
regulation
specific
phases
such
as
RNA
polymerase
II
initiation,
pause–release,
heterogeneity,
consistency.
The
conclusion
from
these
by
itself
regulates
precise
essential
for
normal
development
preventing
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(3), С. 1459 - 1459
Опубликована: Янв. 25, 2024
Mammalian
fertilization
initiates
the
reprogramming
of
oocytes
and
sperm,
forming
a
totipotent
zygote.
During
this
intricate
process,
zygotic
genome
undergoes
maternal-to-zygotic
transition
(MZT)
subsequent
activation
(ZGA),
marking
initiation
transcriptional
control
gene
expression
post-fertilization.
Histone
modifications
are
pivotal
in
shaping
cellular
identity
many
mammals.
Recent
advances
chromatin
analysis
have
enabled
detailed
explorations
histone
during
ZGA.
This
review
delves
into
conserved
unique
regulatory
strategies,
providing
essential
insights
dynamic
changes
their
variants
ZGA
The
objective
is
to
explore
recent
advancements
leading
mechanisms
related
governing
embryonic
development
phase
depth.
These
considerations
will
be
useful
for
informing
future
therapeutic
approaches
that
target
epigenetic
regulation
diverse
biological
contexts.
It
also
contribute
extensive
areas
evolutionary
developmental
biology
possibly
lay
foundation
research
discussion
on
seminal
topic.
Abstract
Secondary
trastuzumab
resistance
represents
an
evolutionary
adaptation
of
HER2‐positive
breast
cancer
during
anti‐HER2
treatment.
Most
current
studies
have
tended
to
prioritize
HER2
and
its
associated
signaling
pathways,
often
overlooking
broader
but
seemingly
less
relevant
cellular
processes,
along
with
their
genetic
epigenetic
mechanisms.
Here,
transcriptome
data
is
not
only
characterized
also
examined
epigenomic
3D
genome
architecture
information
in
both
trastuzumab‐sensitive
secondary‐resistant
cells.
The
findings
reveal
that
the
global
metabolic
reprogramming
may
stem
from
genome‐wide
alterations
histone
modifications
chromatin
structure.
Specifically,
transcriptional
activities
key
genes
involved
lipid
metabolism
appear
be
regulated
by
variant
promoter
H3K27me3
H3K4me3
modifications,
as
well
promoter‐enhancer
interactions.
These
discoveries
offer
valuable
insights
into
how
cells
adapt
anti‐tumor
drugs
potential
impact
future
diagnostic
treatment
strategies.
PLoS ONE,
Год журнала:
2025,
Номер
20(1), С. e0313255 - e0313255
Опубликована: Янв. 9, 2025
INhibitor
of
Growth
(ING1-5)
proteins
are
epigenetic
readers
that
target
histone
acetyltransferase
(HAT)
or
deacetylase
(HDAC)
complexes
to
the
H3K4Me3
mark
active
transcription.
ING5
targets
Moz/Morf
and
HBO1
HAT
alter
acetylation
H3
H4
core
histones,
affecting
gene
expression.
Previous
experiments
in
vitro
indicated
functions
maintain
stem
cell
character
normal
cancer
cells.
Here
we
find
CRISPR/Cas9
knockout
(KO)
mice
sub-fertile
but
show
no
decrease
lifespan
ability
heal
wounds
despite
indications
depleted
pools
several
tissues.
KO
mouse
embryo
fibroblasts
accumulate
G2
cycle,
have
high
levels
abnormal
nuclei
basal
γH2AX
indicator
DNA
damage.
animals
also
develop
severe
dermatitis
at
a
5-fold
higher
rate
wild-type
littermates.
Consistent
with
serving
tumor
suppressive
role,
developed
germinal
centre
diffuse
large
B-cell
lymphomas
6-fold
than
control
18
months
age.
These
data
suggest
vivo
multiple
organs,
reduction
populations
is
not
limiting
for
murine
like
subset
other
ING
family
members,
as
suppressor
hematopoietic
cells
.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 11, 2025
Abstract
Loss
of
epigenetic
information
during
physiological
aging
compromises
cellular
identity,
leading
to
de-repression
developmental
genes.
Here,
we
assessed
the
epigenomic
landscape
vulnerable
neurons
in
two
reference
mouse
models
Huntington
neurodegenerative
disease
(HD),
using
cell-type-specific
multi-omics,
including
temporal
analysis
at
three
stages
via
FANS-CUT&Tag.
We
show
accelerated
genes
HD
striatal
neurons,
involving
histone
re-acetylation
and
depletion
H2AK119
ubiquitination
H3K27
trimethylation
marks,
which
are
catalyzed
by
polycomb
repressive
complexes
1
2
(PRC1
PRC2),
respectively.
further
identify
a
PRC1-dependent
subcluster
bivalent
transcription
factors
that
is
re-activated
neurons.
This
mechanism
likely
involves
progressive
paralog
switching
between
PRC1-CBX
genes,
promotes
upregulation
normally
low-expressed
PRC1-CBX2/4/8
isoforms
alongside
down-regulation
predominant
these
cells
(e.g.,
CBX6/7).
Collectively,
our
data
provide
evidence
for
