Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(8), P. 114593 - 114593
Published: Aug. 1, 2024
We
describe
a
time-resolved
nascent
single-cell
RNA
sequencing
(RNA-seq)
approach
that
measures
gene-specific
transcriptional
noise
and
the
fraction
of
active
genes
in
S.
cerevisiae.
Most
are
expressed
with
near-constitutive
behavior,
while
subset
show
high
mRNA
variance
suggestive
transcription
bursting.
Transcriptional
is
highest
cofactor/coactivator-redundant
(CR)
gene
class
(dependent
on
both
SAGA
TFIID)
strongest
TATA-containing
CR
genes.
Using
this
approach,
we
also
find
histone
switches
from
low-level,
low-noise
constitutive
mode
during
M
M/G1
to
an
activated
state
S
phase
shows
increase
promoters
switch
noisy
bursty
mode.
Rapid
depletion
cofactors
MED
Tail
indicates
factors
play
important
role
stimulating
at
genes,
more
modest
noise.
Trends in Genetics,
Journal Year:
2024,
Volume and Issue:
40(2), P. 160 - 174
Published: Jan. 12, 2024
Recent
imaging
studies
have
captured
the
dynamics
of
regulatory
events
transcription
inside
living
cells.
These
include
factor
(TF)
DNA
binding,
chromatin
remodeling
and
modification,
enhancer-promoter
(E-P)
proximity,
cluster
formation,
preinitiation
complex
(PIC)
assembly.
Together,
these
molecular
culminate
in
stochastic
bursts
RNA
synthesis,
but
their
kinetic
relationship
remains
largely
unclear.
In
this
review,
we
compare
timescales
upstream
steps
(input)
with
kinetics
transcriptional
bursting
(output)
to
generate
mechanistic
models
single
We
highlight
open
questions
potential
technical
advances
guide
future
endeavors
toward
a
quantitative
understanding
regulation.
Cell Reports,
Journal Year:
2022,
Volume and Issue:
41(3), P. 111492 - 111492
Published: Oct. 1, 2022
Transcription
induces
a
wave
of
DNA
supercoiling,
altering
the
binding
affinity
RNA
polymerases
and
reshaping
biochemical
landscape
gene
regulation.
As
supercoiling
rapidly
diffuses,
transcription
dynamically
reshapes
regulation
proximal
genes,
forming
complex
feedback
loop.
However,
theoretical
framework
is
needed
to
integrate
biophysical
with
transcriptional
To
investigate
role
supercoiling-mediated
within
multi-gene
systems,
we
model
under
influence
polymerase
dynamics,
allowing
us
identify
patterns
expression
that
result
from
physical
inter-gene
coupling.
We
find
syntax—the
relative
ordering
orientation
genes—defines
profiles,
variance,
burst
correlation
two-gene
systems.
Furthermore,
can
enhance
or
weaken
Our
results
suggest
couples
behavior
between
neighboring
providing
regulatory
mechanism
tunes
variance
in
engineered
networks
explains
co-localized
native
circuits.
The
role
of
the
spatial
organization
chromosomes
in
directing
transcription
remains
an
outstanding
question
gene
regulation.
Here,
we
analyze
two
recent
single-cell
imaging
methodologies
applied
across
hundreds
genes
to
systematically
contribution
chromosome
conformation
transcriptional
Those
are
(1)
chromatin
tracing
with
super-resolution
fixed
cells;
and
(2)
high-throughput
labeling
nascent
RNA
living
cells.
Specifically,
determine
physical
distance
coordination
bursts.
We
find
that
individual
adopt
a
constrained
reposition
toward
centroid
surrounding
upon
activation.
Leveraging
variability
inherent
imaging,
show
-
but
not
genomic
between
on
is
major
factor
driving
co-bursting.
By
combining
this
analysis
live-cell
arrive
at
corrected
correlation
[Formula:
see
text]
for
separated
by
<
400
nm.
propose
surprisingly
large
represents
property
human
establishes
benchmark
future
experimental
studies.
Torsional
stress
in
chromatin
plays
a
fundamental
role
cellular
functions,
influencing
key
processes
such
as
transcription,
replication,
and
organization.
Transcription
other
may
generate
be
regulated
by
torsional
stress.
In
the
genome,
interplay
of
these
creates
complicated
patterns
both
positive
(+)
negative
(-)
torsion.
However,
challenge
generating
an
accurate
torsion
map
is
determining
zero-torsion
baseline
signal,
which
conflated
with
accessibility.
Here,
we
introduce
high-resolution
method
based
on
intercalator
trimethylpsoralen
(TMP)
to
address
this
challenge.
We
describe
establish
while
preserving
state
genome
S.
cerevisiae
.
This
approach
enables
mapping
accessibility
cell.
Our
analysis
shows
transcription-generated
domains
consistent
twin-supercoiled-domain
model
transcription
suggests
for
recruiting
topoisomerases
regulating
3D
architecture
via
cohesin.
Significantly,
reveal
that
insulator
sequence-specific
factors
decouple
between
divergent
promoters,
whereas
spreads
promoters
lacking
factors,
suggesting
serves
regulatory
mechanism
regions.
Although
insulators
are
known
gene
expression,
our
finding
provides
physical
explanation
how
decoupling
occur.
new
potential
path
forward
using
TMP
measure
without
confounding
contribution
chromatin.
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Feb. 19, 2025
Topoisomerases
are
critical
nuclear
enzymes
that
resolve
DNA
topological
challenges
during
genetic
processes.
However,
there
is
currently
a
lack
of
comprehensive
multi-omics
analysis
TOP2A
from
pan-cancer
perspective,
despite
its
significance.
A
multiomics
was
conducted
to
investigate
across
various
cancer
types.
This
study
involved
the
integration
over
10,000
multidimensional
genomic
datasets
33
distinct
types,
obtained
The
Cancer
Genome
Atlas
(TCGA).
focused
on
evaluating
overall
activity
levels
in
pan-cancers,
which
encompassed
differential
expression,
clinical
significance,
immune
cell
infiltration,
and
regulation
pathways
related
cancer.
Aberrant
epigenetic
modifications
alterations
have
been
identified
as
being
associated
with
dysregulation
expression
levels.
These
molecular
changes
substantial
impacts
progression,
intratumoral
heterogeneity,
immunological
status,
biomarkers.
Consequently,
patient
prognosis
varies
significantly
based
presence
specific
nature
these
alterations.
potential
serve
novel
biomarker
for
may
offer
valuable
insights
into
diagnosis
treatment
Nucleic Acids Research,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 12, 2023
Abstract
Transcription-coupled
supercoiling
of
DNA
is
a
key
factor
in
chromosome
compaction
and
the
regulation
genetic
processes
all
domains
life.
It
has
become
common
knowledge
that,
during
transcription,
DNA-dependent
RNA
polymerase
(RNAP)
induces
positive
ahead
it
(downstream)
negative
supercoils
its
wake
(upstream),
as
rotation
RNAP
around
axis
upon
tracking
helical
groove
gets
constrained
due
to
drag
on
transcript.
Here,
we
experimentally
validate
this
so-called
twin-supercoiled-domain
model
with
vitro
real-time
visualization
at
single-molecule
scale.
Upon
binding
promoter
site
supercoiled
molecule,
merges
into
one
large
pinned
plectoneme
residing
apex.
Transcription
by
real
time
demonstrates
that
up-
downstream
are
generated
simultaneously
equal
portions,
agreement
model.
Experiments
carried
out
presence
RNases
A
H,
revealed
an
additional
viscous
transcript
not
necessary
for
induce
supercoils.
The
latter
results
contrast
current
consensus
simulations
origin
twin-supercoiled
domains,
pointing
mechanistic
cause
underlying
supercoil
generation
transcription.
