The glucocorticoid receptor potentiates aldosterone-induced transcription by the mineralocorticoid receptor
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(47)
Опубликована: Ноя. 14, 2024
The
glucocorticoid
and
mineralocorticoid
receptors
(GR
MR,
respectively)
have
distinct,
yet
overlapping
physiological
pathophysiological
functions.
There
are
indications
that
both
interact
functionally
physically,
but
the
precise
role
of
this
interdependence
is
poorly
understood.
Here,
we
analyzed
impact
GR
coexpression
on
MR
genome-wide
transcriptional
responses
chromatin
binding
upon
activation
by
aldosterone
glucocorticoids,
ligands
receptor.
Transcriptional
in
absence
result
fewer
regulated
genes.
In
contrast,
potentiates
MR-mediated
transcription,
particularly
response
to
aldosterone,
cell
lines
more
physiologically
relevant
model
mouse
colon
organoids.
altered
a
locus-
ligand-specific
way.
Single-molecule
tracking
suggests
presence
contributes
productive
MR/aldosterone
complexes
chromatin.
Together,
our
data
indicate
aldosterone-mediated
activity,
even
glucocorticoids.
Язык: Английский
The plusses and minuses of DNA torsion
eLife,
Год журнала:
2025,
Номер
14
Опубликована: Март 3, 2025
A
new
method
for
mapping
torsion
provides
insights
into
the
ways
that
genome
responds
to
generated
by
RNA
polymerase
II.
Язык: Английский
Identification of Epigenetic Regulators of Fibrotic Transformation in Cardiac Fibroblasts Through Bulk and Single-Cell CRISPR Screens
Опубликована: Апрель 23, 2025
Cardiac
fibrosis
is
mediated
by
the
persistent
activity
of
myofibroblasts,
which
differentiate
from
resident
cardiac
fibroblasts
in
response
to
tissue
damage
and
stress
signals.
The
signaling
pathways
transcription
factors
regulating
fibrotic
transformation
have
been
thoroughly
studied.
In
contrast,
roles
chromatin
myofibroblast
differentiation
their
contribution
pathogenic
remain
poorly
understood.
Here,
we
combined
bulk
single-cell
CRISPR
screens
characterize
primary
fibroblasts.
We
uncover
strong
regulators
states
including
Srcap
Kat5
remodelers.
confirm
that
these
are
required
for
functional
processes
underlying
collagen
synthesis
cell
contractility.
Using
profiling
perturbed
fibroblasts,
demonstrate
pro-fibrotic
complexes
facilitate
well-characterized
factors.
Finally,
show
KAT5
inhibition
alleviates
responses
patient-derived
human
Язык: Английский
Rethinking chromatin accessibility: from compaction to dynamic interactions
Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
90, С. 102299 - 102299
Опубликована: Дек. 19, 2024
Язык: Английский
Hallmarks of glucocorticoid receptor condensates involvement in transcription regulation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 15, 2024
Abstract
Several
proteins
necessary
for
mRNA
production
concentrate
in
intranuclear
condensates,
which
are
proposed
to
affect
transcriptional
output.
The
glucocorticoid
receptor
(GR)
is
a
ligand-activated
transcription
factor
that
regulates
the
expression
of
hundreds
genes
relevant
many
physiological
and
pathological
processes.
As
with
all
members
steroid
family,
GR
forms
condensates
unknown
function.
Here,
we
examine
whether
involved
regulation
using
Airyscan
super-resolution
microscopy
nano-antibodies
targeting
initiation
elongating
states
RNA
polymerase
II
(Pol2).
We
observed
subpopulations
colocalizing
initiating
and,
surprisingly,
Pol2
foci.
analysis
mutants
different
outputs
suggests
correlation
between
condensate
formation
capability
initiation.
Moreover,
number
molecules
within
elongation
appears
be
linked
activity.
Taken
together,
our
data
an
involvement
elongation.
Язык: Английский
Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 9, 2024
SUMMARY
While
the
cohesin
complex
is
a
key
player
in
genome
architecture,
how
it
localizes
to
specific
chromatin
sites
not
understood.
Recently,
we
and
others
have
proposed
that
direct
interactions
with
transcription
factors
lead
localization
of
cohesin-loader
(NIPBL/MAU2)
within
enhancers.
Here,
identify
two
clusters
LxxLL
motifs
NIPBL
sequence
regulate
dynamics,
interactome,
NIPBL-dependent
transcriptional
programs.
One
these
interacts
MAU2
necessary
for
maintenance
NIPBL-MAU2
heterodimer.
The
second
cluster
binds
specifically
ligand-binding
domains
steroid
receptors.
For
glucocorticoid
receptor
(GR),
examine
detail
its
interaction
surfaces
MAU2.
Using
AlphaFold2
molecular
docking
algorithms,
uncover
GR-NIPBL-MAU2
ternary
describe
importance
GR-dependent
gene
regulation.
Finally,
show
multiple
interact
NIPBL-MAU2,
likely
using
interfaces
other
than
those
characterized
GR.
Язык: Английский