Nucleic Acids Research,
Journal Year:
2023,
Volume and Issue:
51(11), P. 5449 - 5468
Published: March 29, 2023
Many
transcription
factors
(TFs)
localize
in
nuclear
clusters
of
locally
increased
concentrations,
but
how
TF
clustering
is
regulated
and
it
influences
gene
expression
not
well
understood.
Here,
we
use
quantitative
microscopy
living
cells
to
study
the
regulation
function
budding
yeast
Gal4
its
endogenous
context.
Our
results
show
that
forms
overlap
with
GAL
loci.
Cluster
number,
density
size
are
different
growth
conditions
by
Gal4-inhibitor
Gal80
concentration.
truncation
mutants
reveal
facilitated
by,
does
completely
depend
on
DNA
binding
intrinsically
disordered
regions.
Moreover,
discover
acts
as
a
double-edged
sword:
self-interactions
aid
recruitment
target
genes,
recruited
molecules
DNA-bound
do
contribute
to,
may
even
inhibit,
activation.
We
propose
need
balance
effects
search
activation
facilitate
proper
expression.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Jan. 1, 2025
Deciphering
how
genes
interpret
information
from
transcription
factor
(TF)
concentrations
within
the
cell
nucleus
remains
a
fundamental
question
in
gene
regulation.
Recent
advancements
have
revealed
heterogeneous
distribution
of
TF
molecules,
posing
challenges
to
precisely
decoding
concentration
signals.
Using
high-resolution
single-cell
imaging
fluorescently
tagged
Bicoid
living
Drosophila
embryos,
we
show
that
accumulation
submicrometer
clusters
preserves
spatial
maternal
gradient.
These
provide
precise
cues
through
intensity,
size,
and
frequency.
We
further
discover
target
colocalize
with
these
an
enhancer-binding
affinity-dependent
manner.
Our
modeling
suggests
clustering
offers
faster
sensing
mechanism
for
global
nuclear
than
freely
diffusing
molecules
detected
by
simple
enhancers.
Current Biology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Highlights•The
Balbiani
forms
in
oogenesis
by
developmental
molecular
condensation
of
Buc•Bb
evolves
from
dynamic,
liquid-like
Buc
granules
to
a
solid,
stable
compartment•Multistep
regulation
microtubules
controls
condensation,
ensuring
polarity•Novel
candidate
regulators,
partners,
and
targets
are
identifiedSummaryVertebrate
oocyte
polarity
has
been
observed
for
two
centuries
is
essential
embryonic
axis
formation
germline
specification,
yet
its
underlying
mechanisms
remain
unknown.
In
polarization,
critical
RNA-protein
(RNP)
delivered
the
oocyte's
vegetal
pole
stored
body
(Bb),
membraneless
organelle
conserved
across
species
insects
humans.
However,
Bb
still
unclear.
Here,
we
elucidate
zebrafish
through
biomolecular
condensation.
Using
super-resolution
microscopy,
live
imaging,
biochemical,
genetic
analyses
vivo,
demonstrate
that
driven
phase
separation
intrinsically
disordered
protein
Bucky
ball
(Buc).
Live
analyses,
fluorescence
recovery
after
photobleaching
(FRAP)
experiments
vivo
reveal
Buc-dependent
changes
condensate's
dynamics
apparent
material
properties,
transitioning
condensates
solid-like
compartment.
Furthermore,
identify
multistep
condensation:
first
dynein-mediated
trafficking
early
condensing
granules,
then
scaffolding
condensed
likely
crowding,
finally
caging
mature
prevent
overgrowth
maintain
shape.
These
regulatory
steps
ensure
single
intact
Bb,
which
considered
polarization
development.
Our
work
offers
insight
into
long-standing
question
origins
non-mammalian
vertebrates,
supports
paradigm
cellular
control
over
microtubules,
highlights
as
key
process
female
reproduction.Graphical
abstract
Critical Reviews in Biochemistry and Molecular Biology,
Journal Year:
2020,
Volume and Issue:
56(1), P. 1 - 16
Published: Nov. 12, 2020
The
focus
of
this
review
is
the
human
de
novo
purine
biosynthetic
pathway.
pathway
enzymes
are
enumerated,
as
well
reactions
they
catalyze
and
their
physical
properties.
Early
literature
evidence
suggested
that
might
assemble
into
a
multi-enzyme
complex
called
metabolon.
finding
fluorescently-tagged
chimeras
form
discrete
puncta,
now
purinosomes,
further
elaborated
in
to
include:
discussion
assembly;
role
ancillary
proteins;
locus
at
microtubule/mitochondria
interface;
elucidation
endogenous
levels,
purinosomes
function
channel
intermediates
from
phosphoribosyl
pyrophosphate
AMP
GMP;
for
exist
protein
condensate.
concludes
with
consideration
probable
signaling
pathways
promote
assembly
disassembly
purinosome,
particular
identification
candidate
kinases
given
extensive
phosphorylation
enzymes.
These
collective
findings
substantiate
our
current
view
metabolon
whose
properties
will
be
representative
how
other
metabolic
organized
function.
