Gene expression and DNA methylation changes in response to hypoxia in toxicant-adapted Atlantic killifish (Fundulus heteroclitus)
Biology Open,
Год журнала:
2025,
Номер
14(1)
Опубликована: Янв. 6, 2025
ABSTRACT
Coastal
fish
populations
are
threatened
by
multiple
anthropogenic
impacts,
including
the
accumulation
of
industrial
contaminants
and
increasing
frequency
hypoxia.
Some
Atlantic
killifish
(Fundulus
heteroclitus),
like
those
in
New
Bedford
Harbor
(NBH),
Massachusetts,
USA,
have
evolved
a
resistance
to
dioxin-like
polychlorinated
biphenyls
(PCBs)
that
may
influence
their
ability
cope
with
secondary
stressors.
To
address
this
question,
we
compared
hepatic
gene
expression
DNA
methylation
patterns
response
mild
or
severe
hypoxia
from
NBH
Scorton
Creek
(SC),
reference
population
relatively
pristine
environment.
We
hypothesized
would
show
altered
responses
due
trade-offs
linked
toxicant
resistance.
Our
results
revealed
substantial
differences
between
populations.
SC
demonstrated
dose-dependent
changes
hypoxia,
while
exhibited
muted
transcriptional
Interestingly,
showed
significant
did
not
exhibit
notable
epigenetic
alterations.
These
findings
suggest
toxicant-adapted
face
molecular
environmental
stress,
potentially
impacting
survive
coastal
habitats.
Further
research
is
needed
elucidate
functional
implications
these
modifications
role
adaptive
stress
responses.
Язык: Английский
Ectopic expression of testis-specific transcription elongation factor in driving cancer
Science Advances,
Год журнала:
2025,
Номер
11(11)
Опубликована: Март 14, 2025
The
testis-specific
BET
protein
BRDT
structurally
resembles
the
ubiquitous
BRD4
and
is
misexpressed
in
cancer,
we
show
that
misexpression
may
affect
lung
cancer
progression.
knockdown
cells
slowed
tumor
growth
prolonged
survival
a
xenograft
model.
Comparative
characterization
of
PTEFb
complex
participation
chromatin
binding
indicates
BRD4-redundant
BRD4-distinct
functions.
Unlike
dual
depletion,
individual
or
did
not
impair
transcriptional
responses
to
hypoxia
BRDT-expressing
cells,
consistent
with
redundant
function.
However,
depletion/BRDT
complementation
revealed
can
also
release
paused
RNA
polymerase
II
independently
its
bromodomains
as
previously
demonstrated
be
required
for
Pol
pause/release
function
BRD4,
underscoring
functional
importance
C-terminal
domains
both
their
potential
therapeutic
targets
solid
tumors.
Based
on
this
study,
future
investigations
should
explore
functions
driving
pathogenesis.
Язык: Английский
A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 18, 2025
Abstract
Severe
acute
hypoxic
stress
is
a
major
contributor
to
the
pathology
of
human
diseases,
including
ischemic
disorders.
Current
treatments
focus
on
managing
consequences
hypoxia,
with
few
addressing
cellular
adaptation
low-oxygen
environments.
Here,
we
investigate
whether
accelerating
hypoxia
could
provide
strategy
alleviate
stress.
We
develop
high-content
phenotypic
screening
platform
identify
compounds
that
fast-track
Our
captures
high-dimensional
response
trajectory
consisting
normoxic,
acutely
stressed,
and
chronically
adapted
cell
states.
Leveraging
this
trajectory,
phenotypically
shift
cells
from
stressed
state
towards
state,
revealing
mTOR/PI3K
or
BET
inhibition
as
strategies
induce
shift.
Importantly,
our
compound
hits
promote
survival
liver
exposed
ischemia-like
stress,
rescue
cardiomyocytes
“phenopushing”
offers
general,
target-agnostic
approach
targets
accelerate
adaptation,
applicable
across
various
conditions.
Язык: Английский
TurboCas: A method for locus-specific labeling of genomic regions and isolating their associated protein interactome
Molecular Cell,
Год журнала:
2024,
Номер
84(24), С. 4929 - 4944.e8
Опубликована: Дек. 1, 2024
Язык: Английский
Gene expression and DNA methylation changes in response to hypoxia in toxicant-adapted Atlantic killifish (Fundulus heteroclitus)
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 2, 2024
Abstract
Coastal
fish
populations
are
threatened
by
multiple
anthropogenic
impacts,
including
the
accumulation
of
industrial
contaminants
and
increasing
frequency
hypoxia.
Some
Atlantic
killifish
(
Fundulus
heteroclitus
),
like
those
in
New
Bedford
Harbor
(NBH),
Massachusetts,
have
evolved
a
resistance
to
dioxin-like
polychlorinated
biphenyls
(PCBs)
that
may
influence
their
ability
cope
with
secondary
stressors.
To
address
this
question,
we
compared
hepatic
gene
expression
DNA
methylation
patterns
response
mild
or
severe
hypoxia
from
NBH
Scorton
Creek
(SC),
reference
population
relatively
pristine
environment.
We
hypothesized
would
show
altered
responses
due
trade-offs
linked
toxicant
resistance.
Our
results
revealed
substantial
differences
between
populations.
SC
demonstrated
dose-dependent
changes
hypoxia,
while
exhibited
muted
transcriptional
Interestingly,
showed
significant
did
not
exhibit
notable
epigenetic
alterations.
These
findings
suggest
toxicant-adapted
face
molecular
environmental
stress,
potentially
impacting
survive
coastal
habitats.
Further
research
is
needed
elucidate
functional
implications
these
modifications
role
adaptive
stress
responses.
Summary
Statement
This
study
reveals
how
toxicants
compromise
respond
highlighting
impact
survival
stressed
environments.
Язык: Английский
The Role of H3K27 acetylation in oxygen-glucose deprivation-induced spinal cord injury and potential for neuroprotective therapies
Brain Research Bulletin,
Год журнала:
2024,
Номер
220, С. 111152 - 111152
Опубликована: Дек. 4, 2024
Spinal
cord
injury
(SCI)
is
a
debilitating
condition
that
often
results
in
paralysis
and
lifelong
medical
challenges.
Research
has
shown
epigenetic
modifications,
particularly
histone
acetylation,
play
role
neuroprotection
following
hypoxic-ischemic
events
SCI.
The
objective
of
this
study
was
to
explore
the
effects
H3K27
along
with
its
underlying
mechanisms,
on
tolerance
hypoxia
ischemia
Язык: Английский