Cell Reports,
Год журнала:
2019,
Номер
26(5), С. 1174 - 1188.e5
Опубликована: Янв. 1, 2019
Neuronal
activity-inducible
gene
transcription
correlates
with
rapid
and
transient
increases
in
histone
acetylation
at
promoters
enhancers
of
activity-regulated
genes.
Exactly
how
modulates
these
genes
has
remained
unknown.
We
used
single-cell
situ
transcriptional
analysis
to
show
that
Fos
Npas4
are
transcribed
stochastic
bursts
mouse
neurons
membrane
depolarization
mRNA
expression
by
increasing
burst
frequency.
then
expressed
dCas9-p300
or
dCas9-HDAC8
fusion
proteins
mimic
block
activity-induced
locally
enhancers.
Adding
increased
prolonging
duration
resulted
higher
protein
levels
an
elevation
resting
potential.
Inhibiting
reduced
reducing
frequency
impaired
experience-dependent
induction
the
hippocampus
vivo.
Thus,
tunes
dynamics
experience-regulated
affect
selective
changes
neuronal
cellular
function.
Abstract
The
epigenetic
modifications
of
histones
are
versatile
marks
that
intimately
connected
to
development
and
disease
pathogenesis
including
human
cancers.
In
this
review,
we
will
discuss
the
many
different
types
histone
biological
processes
with
which
they
involved.
Specifically,
review
enzymatic
machineries
involved
in
cancer
progression,
how
apply
currently
available
small
molecule
inhibitors
for
modifiers
as
tool
compounds
study
functional
significance
their
clinical
implications.
Genes & Development,
Год журнала:
2018,
Номер
32(1), С. 26 - 41
Опубликована: Янв. 1, 2018
Regulation
by
gene-distal
enhancers
is
critical
for
cell
type-specific
and
condition-specific
patterns
of
gene
expression.
Thus,
to
understand
the
basis
activity
in
a
given
type
or
tissue,
we
must
identify
precise
locations
functionally
characterize
their
behaviors.
Here,
demonstrate
that
transcription
nearly
universal
feature
Drosophila
mammalian
cells
nascent
RNA
sequencing
strategies
are
optimal
identification
both
superenhancers.
We
dissect
mechanisms
governing
enhancer
discover
remarkable
similarities
at
protein-coding
genes.
show
polymerase
II
(RNAPII)
undergoes
regulated
pausing
release
enhancers.
However,
as
compared
with
mRNA
genes,
RNAPII
less
stable
more
prone
early
termination.
Furthermore,
found
level
histone
H3
Lys4
(H3K4)
methylation
corresponds
transcriptional
such
highly
active
display
H3K4
trimethylation
rather
than
monomethylation
considered
hallmark
Finally,
our
work
provides
insights
into
unique
characteristics
superenhancers,
which
stimulate
high-level
expression
through
rapid
pause
release;
interestingly,
this
property
renders
associated
genes
resistant
loss
factors
stabilize
paused
RNAPII.
Cell Reports,
Год журнала:
2018,
Номер
24(7), С. 1722 - 1729
Опубликована: Авг. 1, 2018
Acetylation
of
histone
H3
at
lysine
27
is
a
well-defined
marker
enhancer
activity.
However,
the
functional
impact
this
modification
enhancers
poorly
understood.
Here,
we
use
chemical
genetics
approach
to
acutely
block
function
cAMP
response
element
binding
protein
(CREB)
(CBP)/P300
bromodomain
in
models
hematological
malignancies
and
describe
consequent
loss
H3K27Ac
specifically
from
enhancers,
despite
continued
presence
CBP/P300
chromatin.
Using
dissect
role
identify
critical
for
production
RNAs
transcription
enhancer-regulated
gene
networks.
Genes & Development,
Год журнала:
2019,
Номер
33(15-16), С. 903 - 935
Опубликована: Май 23, 2019
As
the
process
that
silences
gene
expression
ensues
during
development,
stage
is
set
for
activity
of
Polycomb-repressive
complex
2
(PRC2)
to
maintain
these
repressed
profiles.
PRC2
catalyzes
a
specific
histone
posttranslational
modification
(hPTM)
fosters
chromatin
compaction.
also
facilitates
inheritance
this
hPTM
through
its
self-contained
“write
and
read”
activities,
key
preserving
cellular
identity
cell
division.
changes
in
occur
without
DNA
sequence
are
inherited,
epigenetic
scope.
Mutants
mammalian
or
substrate
contribute
cancer
other
diseases,
research
into
aberrant
pathways
yielding
viable
candidates
therapeutic
targeting.
The
effectiveness
hinges
on
being
recruited
proper
sites;
however,
resolving
determinants
case
was
not
straightforward
thus
piqued
interest
many
field.
Here,
we
chronicle
latest
advances
toward
exposing
high
maintenance.
