Clinical Epigenetics,
Journal Year:
2021,
Volume and Issue:
13(1)
Published: July 8, 2021
Abstract
Transcriptionally
active
chromatin
is
marked
by
tri-methylation
of
histone
H3
at
lysine
4
(H3K4me3)
located
after
first
exons
and
around
transcription
start
sites.
This
epigenetic
mark
typically
restricted
to
narrow
regions
the
5`end
gene
body,
though
a
small
subset
genes
have
broad
H3K4me3
domain
which
extensively
covers
coding
region.
Although
most
studies
focus
on
mark,
associated
with
plethora
modifications
(e.g.,
acetylated
K27)
therein
termed
domain.
Genes
are
involved
in
cell
identity
essential
functions
clinical
potential
as
biomarkers
for
patient
stratification.
Reducing
expression
may
increase
metastatic
cancer
cells.
Enhancers
super-enhancers
interact
forming
hub
interactions
involving
nucleosome-depleted
regions.
Together,
regulatory
elements
coalesce
factors,
modifying/remodeling
enzymes,
coactivators,
Mediator
and/or
Integrator
complex
into
factory
be
analogous
liquid–liquid
phase-separated
condensate.
The
has
dynamic
structure
supports
frequent
bursts.
In
this
review,
we
present
current
knowledge
domains.
Physiological Reviews,
Journal Year:
2017,
Volume and Issue:
97(3), P. 1045 - 1087
Published: May 25, 2017
Estrogen
receptor
alpha
(ERα)
has
been
recognized
now
for
several
decades
as
playing
a
key
role
in
reproduction
and
exerting
functions
numerous
nonreproductive
tissues.
In
this
review,
we
attempt
to
summarize
the
vitro
studies
that
are
basis
of
our
current
understanding
mechanisms
action
ERα
nuclear
roles
played
by
its
two
activation
(AFs)
transcriptional
activities.
We
then
depict
consequences
selective
inactivation
these
AFs
mouse
models,
focusing
on
prominent
reproductive
tract
vascular
system.
Evidence
accumulated
over
last
is
also
associated
with
plasma
membrane
activates
non-nuclear
signaling
from
site.
These
rapid/nongenomic/membrane-initiated
steroid
signals
(MISS)
have
characterized
variety
cell
lines,
particular
endothelial
cells.
The
development
pharmacological
tools
specifically
activate
MISS
generation
mice
expressing
an
protein
impeded
localization
begun
unravel
physiological
vivo.
Finally,
discuss
novel
perspectives
design
tissue-selective
ER
modulators
based
integration
pathophysiological
actions
estrogens.
Enhancers
are
important
regulatory
elements
that
can
control
gene
activity
across
vast
genetic
distances.
However,
the
underlying
nature
of
this
regulation
remains
obscured
because
it
has
been
difficult
to
observe
in
living
cells.
Here,
we
visualize
spatial
organization
and
transcriptional
output
key
pluripotency
regulator
Sox2
its
essential
enhancer
Control
Region
(SCR)
embryonic
stem
cells
(ESCs).
We
find
SCR
show
no
evidence
enhanced
proximity
dynamics
pair
is
limited
over
tens
minutes.
transcription
occurs
short,
intermittent
bursts
ESCs
and,
intriguingly,
demonstrates
association
with
proximity,
suggesting
direct
enhancer-promoter
contacts
do
not
drive
contemporaneous
transcription.
Our
study
establishes
a
framework
for
interrogation
function
supports
an
unexpected
mechanism
expression
uncouples
from
proximity.
Molecular Cell,
Journal Year:
2019,
Volume and Issue:
76(3), P. 473 - 484.e7
Published: Sept. 4, 2019
Highlights•Super-resolution
microscopy
reveals
increased
enhancer-promoter
separation
upon
activation•Synthetic
enhancer
activation
supports
decreased
proximity•Enhancer-promoter
can
be
driven
by
poly(ADP-ribose)
polymerase
1SummaryEnhancers
regulate
the
promoters
of
their
target
genes
over
very
large
genomic
distances.
It
is
widely
assumed
that
mechanisms
action
involve
reorganization
three-dimensional
chromatin
architecture,
but
this
poorly
understood.
The
predominant
model
involves
physical
interaction
looping
out
intervening
chromatin.
However,
studying
enhancer-driven
Sonic
hedgehog
gene
(Shh),
we
have
identified
a
change
in
chromosome
conformation
incompatible
with
simple
model.
Using
super-resolution
3D-FISH
and
capture,
observe
spatial
proximity
between
Shh
its
enhancers
during
differentiation
embryonic
stem
cells
to
neural
progenitors.
We
show
recapitulated
synthetic
activation,
impeded
chromatin-bound
proteins
located
promoter,
appears
catalytic
activity
poly
(ADP-ribose)
polymerase.
Our
data
suggest
models
communication
need
encompass
conformations
other
than
looping.Graphical
abstract
