bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 15, 2024
ABSTRACT
Steroid
receptors
are
involved
in
a
wide
array
of
crosstalk
mechanisms
that
regulate
diverse
biological
processes,
with
significant
implications
diseases,
particularly
cancers.
In
prostate
cancer,
indirect
between
androgen
receptor
(AR)
and
glucocorticoid
(GR)
is
well-documented,
where
GR
replaces
antiandrogen-inactivated
AR
becoming
the
disease
driver.
However,
existence
impact
direct
chromatin
cancer
have
remained
elusive.
Our
genome-wide
investigations
reveal
activation
significantly
expands
binding.
Mechanistically,
induces
remodeling
closed
sites,
facilitating
binding
to
inaccessible
sites.
Importantly,
coactivation
results
distinct
transcriptional
responses
at
both
cell
population
single-cell
levels.
Intriguingly,
pathways
affected
by
these
changes
generally
associated
improved
patient
survival.
Thus,
yields
markedly
different
outcomes
from
known
role
circumventing
blockade
antiandrogens.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Фев. 16, 2024
Whether
phase-separation
is
involved
in
the
organization
of
transcriptional
machinery
and
if
it
aids
or
inhibits
process
a
matter
intense
debate.
In
this
Mini
Review,
we
will
cover
current
knowledge
regarding
role
condensates
on
gene
expression
regulation.
We
summarize
latest
discoveries
relationship
between
condensate
formation,
genome
organization,
activity,
focusing
strengths
weaknesses
experimental
approaches
used
to
interrogate
these
aspects
transcription
living
cells.
Finally,
discuss
challenges
for
future
research.
Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(4), С. 820 - 826
Опубликована: Апрель 25, 2024
Abstract
Eukaryotic
transcription,
a
fundamental
process
that
governs
cell-specific
gene
expression,
has
long
been
the
subject
of
extensive
investigations
in
fields
molecular
biology,
biochemistry,
and
structural
biology.
Recent
advances
microscopy
techniques
have
led
to
fascinating
concept
known
as
“transcriptional
condensates.”
These
dynamic
assemblies
are
result
phenomenon
called
liquid‒liquid
phase
separation,
which
is
driven
by
multivalent
interactions
between
constituent
proteins
cells.
The
essential
associated
with
transcription
concentrated
transcriptional
condensates.
studies
shed
light
on
temporal
dynamics
condensates
their
potential
role
enhancing
efficiency
transcription.
In
this
article,
we
explore
properties
condensates,
investigate
how
they
evolve
over
time,
evaluate
significant
impact
Furthermore,
highlight
innovative
allow
us
manipulate
these
thus
demonstrating
responsiveness
cellular
signals
connection
bursting.
As
our
understanding
continues
grow,
poised
revolutionize
eukaryotic
regulation.
Trends in Biochemical Sciences,
Год журнала:
2024,
Номер
49(5), С. 431 - 444
Опубликована: Фев. 29, 2024
The
glucocorticoid
receptor
(GR)
is
a
major
nuclear
(NR)
drug
target
for
the
treatment
of
inflammatory
disorders
and
several
cancers.
Despite
effectiveness
GR
ligands,
their
systemic
action
triggers
plethora
side
effects,
limiting
long-term
use.
Here,
we
discuss
new
concepts
insights
into
mechanisms
to
assist
in
identification
routes
toward
enhanced
therapeutic
benefits.
We
zoom
on
communication
between
different
domains
how
this
influenced
by
ligands.
detail
findings
interaction
chromatin,
highlight
condensate
formation
coregulator
confinement
can
perturb
transcriptional
responses.
Last,
potential
novel
ligands
exploitation
crosstalk
with
other
NRs.
Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
86, С. 102191 - 102191
Опубликована: Апрель 4, 2024
To
make
a
multicellular
organism,
genes
need
to
be
transcribed
at
the
right
developmental
stages
and
in
tissues.
DNA
sequences
termed
'enhancers'
are
crucial
achieve
this.
Despite
concerted
efforts,
exact
mechanisms
of
enhancer
activity
remain
elusive.
Mixed
lineage
leukemia
(MLL
or
KMT2A)
rearrangements
(MLLr),
commonly
observed
cases
acute
lymphoblastic
(ALL)
myeloid
leukemia,
produce
novel
in-frame
fusion
proteins.
Recent
work
has
shown
that
MLL-AF4
protein
drives
aberrant
key
oncogenes
ALL,
dependent
on
continued
presence
complex
components.
As
well
as
providing
some
general
insights
into
function,
these
observations
may
also
provide
an
explanation
for
transcriptional
heterogeneity
MLLr
patients.
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Март 3, 2025
Abstract
Transcriptional
dysregulation
is
a
hallmark
of
cancer
initiation
and
progression,
driven
by
genetic
epigenetic
alterations.
Enhancer
reprogramming
has
emerged
as
pivotal
driver
carcinogenesis,
with
cells
often
relying
on
aberrant
transcriptional
programs.
The
advent
high-throughput
sequencing
technologies
provided
critical
insights
into
enhancer
events
their
role
in
malignancy.
While
targeting
enhancers
presents
promising
therapeutic
strategy,
significant
challenges
remain.
These
include
the
off-target
effects
enhancer-targeting
technologies,
complexity
redundancy
networks,
dynamic
nature
reprogramming,
which
may
contribute
to
resistance.
This
review
comprehensively
encapsulates
structural
attributes
enhancers,
delineates
mechanisms
underlying
malignant
transformation,
evaluates
opportunities
limitations
associated
cancer.
