Cells,
Journal Year:
2023,
Volume and Issue:
12(5), P. 798 - 798
Published: March 3, 2023
The
Hypoxia
Inducible
Factor
1
(HIF-1)
plays
a
major
role
in
the
cellular
response
to
hypoxia
by
regulating
expression
of
many
genes
involved
adaptive
processes
that
allow
cell
survival
under
low
oxygen
conditions.
Adaptation
hypoxic
tumor
micro-environment
is
also
critical
for
cancer
proliferation
and
therefore
HIF-1
considered
valid
therapeutical
target.
Despite
huge
progress
understanding
regulation
activity
levels
or
oncogenic
pathways,
way
interacts
with
chromatin
transcriptional
machinery
order
activate
its
target
still
matter
intense
investigation.
Recent
studies
have
identified
several
different
HIF-1-
chromatin-associated
co-regulators
play
important
roles
general
HIF-1,
independent
levels,
as
well
selection
binding
sites,
promoters
genes,
which,
however,
often
depends
on
context.
We
review
here
these
examine
their
effect
compilation
well-characterized
direct
assess
range
involvement
hypoxia.
Delineating
mode
significance
interaction
between
associated
may
offer
new
attractive
specific
targets
anticancer
therapy.
Science,
Journal Year:
2018,
Volume and Issue:
361(6400)
Published: June 21, 2018
Super-enhancers
(SEs)
are
clusters
of
enhancers
that
cooperatively
assemble
a
high
density
the
transcriptional
apparatus
to
drive
robust
expression
genes
with
prominent
roles
in
cell
identity.
Here
we
demonstrate
SE-enriched
coactivators
BRD4
and
MED1
form
nuclear
puncta
at
SEs
exhibit
properties
liquid-like
condensates
disrupted
by
chemicals
perturb
condensates.
The
intrinsically
disordered
regions
(IDRs)
can
phase-separated
droplets,
MED1-IDR
droplets
compartmentalize
concentrate
transcription
from
extracts.
These
results
support
idea
apparatus,
suggest
role
for
coactivator
IDRs
this
process,
offer
insights
into
mechanisms
involved
control
key
cell-identity
genes.
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
Genome biology,
Journal Year:
2021,
Volume and Issue:
22(1)
Published: April 15, 2021
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.
Open Biology,
Journal Year:
2018,
Volume and Issue:
8(9)
Published: Sept. 1, 2018
Since
their
characterization
as
conserved
modules
that
regulate
progression
through
the
eukaryotic
cell
cycle,
cyclin-dependent
protein
kinases
(CDKs)
in
higher
cells
are
now
also
emerging
significant
regulators
of
transcription,
metabolism
and
differentiation.
The
cyclins,
though
originally
characterized
CDK
partners,
have
CDK-independent
roles
include
regulation
DNA
damage
repair
transcriptional
programmes
direct
differentiation,
apoptosis
metabolic
flux.
This
review
compares
structures
members
cyclin
families
determined
by
X-ray
crystallography,
considers
what
mechanistic
insights
they
provide
to
guide
functional
studies
distinguish
CDK-
cyclin-specific
activities.
Aberrant
activity
is
a
hallmark
number
diseases,
structural
can
important
identify
novel
routes
therapy.
