Current Opinion in Genetics & Development,
Journal Year:
2023,
Volume and Issue:
79, P. 102022 - 102022
Published: Feb. 25, 2023
Gene
expression
patterns
in
complex
multicellular
organisms
are
regulated
by
enhancers,
which
communicate
with
their
target
gene
promoters
three-dimensional
(3D)
chromatin
structures.
Despite
advances
our
understanding
of
the
mechanisms
that
organize
mammalian
genomes
into
compartments
and
topologically
associating
domains
(TADs),
it
is
not
well
understood
how
specific
interactions
between
enhancers
controlled
this
3D
context.
In
review,
we
give
an
overview
recent
evidence
shows
a
process
loop
extrusion
plays
important
role
regulation
enhancer-promoter
communication
discuss
insights
molecular
mechanism
contributes
to
enhancer-mediated
activation.
Nature Genetics,
Journal Year:
2022,
Volume and Issue:
54(12), P. 1919 - 1932
Published: Dec. 1, 2022
It
remains
unclear
why
acute
depletion
of
CTCF
(CCCTC-binding
factor)
and
cohesin
only
marginally
affects
expression
most
genes
despite
substantially
perturbing
three-dimensional
(3D)
genome
folding
at
the
level
domains
structural
loops.
To
address
this
conundrum,
we
used
high-resolution
Micro-C
nascent
transcript
profiling
in
mouse
embryonic
stem
cells.
We
find
that
enhancer-promoter
(E-P)
interactions
are
largely
insensitive
to
(3-h)
CTCF,
or
WAPL.
YY1
has
been
proposed
as
a
regulator
E-P
loops,
but
also
had
minimal
effects
on
transcription
3D
folding.
Strikingly,
live-cell,
single-molecule
imaging
revealed
reduced
factor
(TF)
binding
chromatin.
Thus,
although
cohesin,
WAPL
is
not
required
for
short-term
maintenance
gene
expression,
our
results
suggest
may
facilitate
TFs
search
bind
their
targets
more
efficiently.
Nature Structural & Molecular Biology,
Journal Year:
2022,
Volume and Issue:
29(6), P. 563 - 574
Published: June 1, 2022
Abstract
Developmental
gene
expression
is
often
controlled
by
distal
regulatory
DNA
elements
called
enhancers.
Distant
enhancer
action
restricted
to
structural
chromosomal
domains
that
are
flanked
CTCF-associated
boundaries
and
formed
through
cohesin
chromatin
loop
extrusion.
To
better
understand
how
enhancers,
genes
CTCF
together
form
control
expression,
we
used
a
bottom-up
approach,
building
series
of
active
landscapes
in
inactive
chromatin.
We
demonstrate
here
transcription
levels
activity
over
time
reduce
with
increased
distance.
The
recruits
stimulate
domain
formation
engage
flanking
sites
formation.
It
requires
exclusively
for
the
activation
distant
genes,
not
proximal
nearby
supporting
efficient
long-range
action.
Our
work
supports
dual
model
enhancers:
its
classic
role
stimulating
initiation
elongation
from
target
promoters
recruiting
creation
domains,
engagement
looping
genes.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Jan. 11, 2021
Abstract
Enhancers
are
DNA
sequences
that
enable
complex
temporal
and
tissue-specific
regulation
of
genes
in
higher
eukaryotes.
Although
it
is
not
entirely
clear
how
enhancer-promoter
interactions
can
increase
gene
expression,
this
proximity
has
been
observed
multiple
systems
at
loci
thought
to
be
essential
for
the
maintenance
expression.
Bromodomain
Extra-Terminal
domain
(BET)
Mediator
proteins
have
shown
capable
forming
phase
condensates
super-enhancer
function.
Here,
we
show
targeting
cells
with
inhibitors
BET
or
pharmacological
degradation
protein
Bromodomain-containing
4
(BRD4)
a
strong
impact
on
transcription
but
very
little
interactions.
Dissolving
reduces
BRD4
binding
enhancers
also
strongly
affect
transcription,
without
disrupting
These
results
suggest
activation
separable
events.
Our
findings
further
indicate
dependent
high
levels
Mediator,
likely
maintained
by
set
factors
including
additional
activator
complexes
and,
some
sites,
CTCF
cohesin.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: April 19, 2022
Abstract
Enhancers
and
promoters
predominantly
interact
within
large-scale
topologically
associating
domains
(TADs),
which
are
formed
by
loop
extrusion
mediated
cohesin
CTCF.
However,
it
is
unclear
whether
complex
chromatin
structures
exist
at
sub-kilobase-scale
to
what
extent
fine-scale
regulatory
interactions
depend
on
extrusion.
To
address
these
questions,
we
present
an
MNase-based
chromosome
conformation
capture
(3C)
approach,
has
enabled
us
generate
the
most
detailed
local
interaction
data
date
(20
bp
resolution)
precisely
investigate
effects
of
CTCF
depletion
architecture.
Our
reveal
that
cis
-regulatory
elements
have
distinct
internal
nano-scale
structures,
insulation
dependent
CTCF,
but
independent
cohesin.
In
contrast,
find
causes
a
subtle
reduction
in
longer-range
enhancer-promoter
can
cause
rewiring
contacts.
Together,
our
show
not
essential
for
interactions,
contributes
their
robustness
specificity
precise
regulation
gene
expression.
Cohesin
and
CTCF
are
major
drivers
of
3D
genome
organization,
but
their
role
in
neurons
is
still
emerging.
Here,
we
show
a
prominent
for
cohesin
the
expression
genes
that
facilitate
neuronal
maturation
homeostasis.
Unexpectedly,
observed
two
classes
activity-regulated
with
distinct
reliance
on
mouse
primary
cortical
neurons.
Immediate
early
(IEGs)
remained
fully
inducible
by
KCl
BDNF,
short-range
enhancer-promoter
contacts
at
IEGs
Cell Reports,
Journal Year:
2023,
Volume and Issue:
42(4), P. 112068 - 112068
Published: April 1, 2023
The
spatiotemporal
control
of
gene
expression
is
dependent
on
the
activity
cis-acting
regulatory
sequences,
called
enhancers,
which
regulate
target
genes
over
variable
genomic
distances
and,
often,
by
skipping
intermediate
promoters,
suggesting
mechanisms
that
enhancer-promoter
communication.
Recent
genomics
and
imaging
technologies
have
revealed
highly
complex
interaction
networks,
whereas
advanced
functional
studies
started
interrogating
forces
behind
physical
communication
among
multiple
enhancers
promoters.
In
this
review,
we
first
summarize
our
current
understanding
factors
involved
in
communication,
with
a
particular
focus
recent
papers
new
layers
complexities
to
old
questions.
second
part
subset
connected
"hubs"
discuss
their
potential
functions
signal
integration
regulation,
as
well
putative
might
determine
dynamics
assembly.