Genes & Development,
Journal Year:
2019,
Volume and Issue:
33(23-24), P. 1619 - 1634
Published: Oct. 8, 2019
The
idea
that
liquid–liquid
phase
separation
(LLPS)
may
be
a
general
mechanism
by
which
molecules
in
the
complex
cellular
milieu
self-organize
has
generated
much
excitement
and
fervor
cell
biology
community.
While
this
concept
is
not
new,
its
rise
to
preeminence
resulted
renewed
interest
mechanisms
shape
drive
diverse
self-assembly
processes
from
gene
expression
division
stress
responses.
In
vitro
biochemical
data
have
been
instrumental
deriving
some
of
fundamental
principles
molecular
grammar
biological
separate,
basis
these
interactions.
Definitive
evidence
lacking
as
whether
same
apply
physiological
environment
inside
living
cells.
Perspective,
we
analyze
supporting
vivo
across
multiple
processes.
We
find
for
LLPS
often
phenomenological
inadequate
discriminate
between
other
possible
mechanisms.
Moreover,
causal
relationship
functional
consequences
are
even
more
elusive.
underscore
importance
performing
quantitative
measurements
on
proteins
their
endogenous
state
abundance,
well
make
recommendations
experiments
yield
conclusive
results.
Science,
Journal Year:
2017,
Volume and Issue:
357(6357)
Published: Sept. 21, 2017
Phase
transitions
are
ubiquitous
in
nonliving
matter,
and
recent
discoveries
have
shown
that
they
also
play
a
key
role
within
living
cells.
Intracellular
liquid-liquid
phase
separation
is
thought
to
drive
the
formation
of
condensed
liquid-like
droplets
protein,
RNA,
other
biomolecules,
which
form
absence
delimiting
membrane.
Recent
studies
elucidated
many
aspects
molecular
interactions
underlying
these
remarkable
way
such
dictate
their
material
properties,
composition,
behavior.
Here,
we
review
exciting
developments
highlight
remaining
challenges,
particularly
ability
liquid
condensates
both
facilitate
respond
biological
function
how
metastability
may
underlie
devastating
protein
aggregation
diseases.
Science,
Journal Year:
2018,
Volume and Issue:
361(6400)
Published: June 21, 2018
Super-enhancers
(SEs)
are
clusters
of
enhancers
that
cooperatively
assemble
a
high
density
the
transcriptional
apparatus
to
drive
robust
expression
genes
with
prominent
roles
in
cell
identity.
Here
we
demonstrate
SE-enriched
coactivators
BRD4
and
MED1
form
nuclear
puncta
at
SEs
exhibit
properties
liquid-like
condensates
disrupted
by
chemicals
perturb
condensates.
The
intrinsically
disordered
regions
(IDRs)
can
phase-separated
droplets,
MED1-IDR
droplets
compartmentalize
concentrate
transcription
from
extracts.
These
results
support
idea
apparatus,
suggest
role
for
coactivator
IDRs
this
process,
offer
insights
into
mechanisms
involved
control
key
cell-identity
genes.
Science,
Journal Year:
2018,
Volume and Issue:
361(6400), P. 412 - 415
Published: June 21, 2018
Models
of
gene
control
have
emerged
from
genetic
and
biochemical
studies,
with
limited
consideration
the
spatial
organization
dynamics
key
components
in
living
cells.
We
used
live-cell
superresolution
light-sheet
imaging
to
study
Mediator
coactivator
RNA
polymerase
II
(Pol
II)
directly.
Pol
each
form
small
transient
large
stable
clusters
embryonic
stem
are
colocalized
clusters,
which
associate
chromatin,
properties
phase-separated
condensates,
sensitive
transcriptional
inhibitors.
suggest
that
Mediator,
recruited
by
transcription
factors
at
or
clustered
enhancer
elements,
interact
condensates
vivo.
Science,
Journal Year:
2018,
Volume and Issue:
362(6413)
Published: Oct. 26, 2018
The
spatial
organization
of
chromatin
is
pivotal
for
regulating
genome
functions.
We
report
an
imaging
method
tracing
with
kilobase-
and
nanometer-scale
resolution,
unveiling
conformation
across
topologically
associating
domains
(TADs)
in
thousands
individual
cells.
Our
data
revealed
TAD-like
structures
globular
sharp
domain
boundaries
single
varied
from
cell
to
cell,
occurring
nonzero
probabilities
at
all
genomic
positions
but
preferentially
CCCTC-binding
factor
(CTCF)-
cohesin-binding
sites.
Notably,
cohesin
depletion,
which
abolished
TADs
the
population-average
level,
did
not
diminish
cells
eliminated
preferential
boundary
positions.
Moreover,
we
observed
widespread,
cooperative,
multiway
interactions,
remained
after
depletion.
These
results
provide
critical
insight
into
mechanisms
underlying
hub
formation.
