Cell Death Discovery,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: March 3, 2025
Abstract
Transcriptional
dysregulation
is
a
hallmark
of
cancer
initiation
and
progression,
driven
by
genetic
epigenetic
alterations.
Enhancer
reprogramming
has
emerged
as
pivotal
driver
carcinogenesis,
with
cells
often
relying
on
aberrant
transcriptional
programs.
The
advent
high-throughput
sequencing
technologies
provided
critical
insights
into
enhancer
events
their
role
in
malignancy.
While
targeting
enhancers
presents
promising
therapeutic
strategy,
significant
challenges
remain.
These
include
the
off-target
effects
enhancer-targeting
technologies,
complexity
redundancy
networks,
dynamic
nature
reprogramming,
which
may
contribute
to
resistance.
This
review
comprehensively
encapsulates
structural
attributes
enhancers,
delineates
mechanisms
underlying
malignant
transformation,
evaluates
opportunities
limitations
associated
cancer.
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.
Nucleus,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: May 22, 2023
Transcription
is
the
fundamental
process
of
gene
expression,
which
in
eukaryotes
occurs
within
complex
physicochemical
environment
nucleus.
Decades
research
have
provided
extreme
detail
molecular
and
functional
mechanisms
transcription,
but
spatial
genomic
organization
transcription
remains
mysterious.
Recent
discoveries
show
that
transcriptional
components
can
undergo
phase
separation
create
distinct
compartments
inside
nucleus,
providing
new
models
through
to
view
eukaryotes.
In
this
review,
we
focus
on
condensates
their
separation-like
behaviors.
We
suggest
differentiation
between
physical
descriptions
dynamic
biomolecular
assemblies
required
for
productive
discuss
how
are
central
organizing
three-dimensional
genome
across
temporal
scales.
Finally,
map
approaches
therapeutic
manipulation
ask
what
technical
advances
needed
understand
more
completely.
Current Opinion in Genetics & Development,
Journal Year:
2024,
Volume and Issue:
85, P. 102159 - 102159
Published: Feb. 20, 2024
Chromosome
structure
regulates
DNA-templated
processes
such
as
transcription
of
genes.
Dynamic
changes
to
chromosome
occur
during
development
and
in
disease
contexts.
The
cohesin
complex
is
a
molecular
motor
that
by
generating
DNA
loops
bring
two
distal
genomic
sites
into
close
spatial
proximity.
There
are
many
open
questions
regarding
the
formation
dissolution
loops,
well
role(s)
regulating
interphase
genome.
This
review
focuses
on
recent
discoveries
provide
insights
role
gene
disease.
Current Opinion in Genetics & Development,
Journal Year:
2025,
Volume and Issue:
90, P. 102303 - 102303
Published: Jan. 14, 2025
Enhancers
in
metazoan
genomes
are
known
to
activate
their
target
genes
across
both
short
and
long
genomic
distances.
Recent
advances
chromosome
conformation
capture
assays
single-cell
imaging
have
shed
light
on
the
underlying
chromatin
contacts
dynamics.
Yet
relationship
between
3D
physical
enhancer-promoter
(E-P)
interactions
transcriptional
activation
remains
unresolved.
In
this
brief
review,
we
discuss
recent
studies
exploring
scales:
from
developmental
stages
minutes
surrounding
tissue
level
single-allele
subcellular
We
how
seemingly
contradictory
observations
might
be
reconciled
contribute
a
refined
causal
E-P
transcription,
with
mutual
influences.
Nature Cancer,
Journal Year:
2024,
Volume and Issue:
5(11), P. 1697 - 1712
Published: Oct. 30, 2024
Abstract
Although
three-dimensional
(3D)
genome
architecture
is
crucial
for
gene
regulation,
its
role
in
disease
remains
elusive.
We
traced
the
evolution
and
malignant
transformation
of
colorectal
cancer
(CRC)
by
generating
high-resolution
chromatin
conformation
maps
33
colon
samples
spanning
different
stages
early
neoplastic
growth
persons
with
familial
adenomatous
polyposis
(FAP).
Our
analysis
revealed
a
substantial
progressive
loss
genome-wide
cis-regulatory
connectivity
at
malignancy
stages,
correlating
nonlinear
regulation
effects.
Genes
high
promoter–enhancer
(P–E)
unaffected
mucosa
were
not
linked
to
elevated
baseline
expression
but
tended
be
upregulated
advanced
stages.
Inhibiting
highly
connected
promoters
preferentially
represses
CRC
cells
compared
normal
colonic
epithelial
cells.
results
suggest
two-phase
model
whereby
reduces
P–E
from
redundant
state
rate-limiting
one
transcriptional
levels,
highlighting
intricate
interplay
between
3D
during
progression.
Communications Biology,
Journal Year:
2025,
Volume and Issue:
8(1)
Published: Jan. 9, 2025
Uncoupling
protein
1
(UCP1)
is
a
crucial
located
in
the
mitochondrial
inner
membrane
that
mediates
nonshivering
thermogenesis.
However,
molecular
mechanisms
by
which
enhancer–promoter
chromatin
interactions
control
Ucp1
transcriptional
regulation
brown
adipose
tissue
(BAT)
are
unclear.
Here,
we
employed
circularized
chromosome
conformation
capture
coupled
with
next-generation
sequencing
(4C-seq)
to
generate
high-resolution
interaction
profiles
of
interscapular
(iBAT)
and
epididymal
white
(eWAT)
revealed
marked
changes
between
iBAT
eWAT.
Next,
identified
four
iBAT-specific
active
enhancers
Ucp1,
three
them
were
activated
cold
stimulation.
Transcriptional
repression
Ucp1-En4
or
Ucp1-En6
region
significantly
downregulated
impaired
function
adipocytes.
Furthermore,
depletion
cohesin
subunit
RAD21
decreased
intensity
promoter
Ucp1.
EBF2
cooperated
acetyltransferase
CBP
regulate
activity
increase
activity.
In
vivo,
lentivirus-mediated
was
injected
into
iBAT,
resulting
impacted
thermogenic
capacity
under
acclimation
conditions.
Studying
functional
regulating
expression
will
provide
important
insights
regulatory
BAT
Chromatin
profiling
reveals
how
enhancer-promoter
tissue,
highlighting
key
driving
thermogenesis
