Transcriptional
rates
are
often
estimated
by
fitting
the
distribution
of
mature
mRNA
numbers
measured
using
smFISH
(single
molecule
fluorescence
in
situ
hybridization)
with
predicted
telegraph
model
gene
expression,
which
defines
two
promoter
states
activity
and
inactivity.
However,
fluctuations
strongly
affected
processes
downstream
transcription.
In
addition,
assumes
one
copy
but
experiments,
cells
may
have
copies
as
replicate
their
genome
during
cell
cycle.
While
it
is
presumed
that
post-transcriptional
noise
number
variation
affect
transcriptional
parameter
estimation,
size
error
introduced
remains
unclear.
To
address
this
issue,
here
we
measure
both
nascent
distributions
GAL10
yeast
classify
each
according
to
its
cycle
phase.
We
infer
parameters
from
distributions,
without
accounting
for
phase
compare
results
live-cell
transcription
measurements
same
gene.
find
that:
(i)
correcting
dynamics
decreases
switching
initiation
rate,
increases
fraction
time
spent
active
state,
well
burst
size;
(ii)
additional
correction
leads
further
a
large
reduction
errors
estimation.
Furthermore,
outline
how
correctly
adjust
measurement
due
uncertainty
site
localisation
when
introns
cannot
be
labelled.
Simulations
data,
corrected
phases
noise,
autocorrelation
functions
agree
those
obtained
imaging.
Abstract
Differential
gene
expression
mechanisms
ensure
cellular
differentiation
and
plasticity
to
shape
ontogenetic
phylogenetic
diversity
of
cell
types.
A
key
regulator
differential
programs
are
the
enhancers,
gene-distal
cis
-regulatory
sequences
that
govern
spatiotemporal
quantitative
dynamics
target
genes.
Enhancers
widely
believed
physically
contact
promoters
effect
transcriptional
activation.
However,
our
understanding
full
complement
regulatory
proteins
definitive
mechanics
enhancer
action
is
incomplete.
Here,
we
review
recent
findings
present
some
emerging
concepts
on
also
outline
a
set
outstanding
questions.
Genes & Development,
Год журнала:
2020,
Номер
34(7-8), С. 465 - 488
Опубликована: Апрель 1, 2020
RNA
polymerase
II
(Pol
II)
transcribes
all
protein-coding
genes
and
many
noncoding
RNAs
in
eukaryotic
genomes.
Although
Pol
is
a
complex,
12-subunit
enzyme,
it
lacks
the
ability
to
initiate
transcription
cannot
consistently
transcribe
through
long
DNA
sequences.
To
execute
these
essential
functions,
an
array
of
proteins
protein
complexes
interact
with
regulate
its
activity.
In
this
review,
we
detail
structure
mechanism
over
dozen
factors
that
govern
initiation
(e.g.,
TFIID,
TFIIH,
Mediator),
pausing,
elongation
DSIF,
NELF,
PAF,
P-TEFb).
The
structural
basis
for
regulation
has
advanced
rapidly
past
decade,
largely
due
technological
innovations
cryoelectron
microscopy.
Here,
summarize
wealth
functional
data
have
enabled
deeper
understanding
mechanisms;
also
highlight
mechanistic
questions
remain
unanswered
or
controversial.
Annual Review of Biochemistry,
Год журнала:
2020,
Номер
89(1), С. 189 - 212
Опубликована: Март 25, 2020
Transcription
in
several
organisms
from
certain
bacteria
to
humans
has
been
observed
be
stochastic
nature:
toggling
between
active
and
inactive
states.
Periods
of
nascent
RNA
synthesis
known
as
bursts
represent
individual
gene
activation
events
which
multiple
polymerases
are
initiated.
Therefore,
bursting
is
the
single
locus
illustration
both
repression.
Although
transcriptional
was
originally
decades
ago,
only
recently
have
technological
advances
enabled
field
begin
elucidating
regulation
at
single-locus
level.
In
this
review,
we
focus
on
how
biochemical,
genomic,
single-cell
data
describe
regulatory
steps
bursts.
