Science Advances,
Journal Year:
2024,
Volume and Issue:
10(17)
Published: April 24, 2024
Polycomb
group
(PcG)
proteins
mediate
epigenetic
silencing
of
important
developmental
genes
by
modifying
histones
and
compacting
chromatin
through
two
major
protein
complexes,
PRC1
PRC2.
These
complexes
are
recruited
to
DNA
CpG
islands
(CGIs)
in
mammals
response
elements
(PREs)
Drosophila
.
When
PcG
target
turned
OFF,
bind
PREs
or
CGIs,
serve
as
anchors
that
loop
together
stabilize
gene
silencing.
Here,
we
address
which
whether
looping
when
their
targets
the
ON
transcriptional
state.
While
binding
most
decreases
at
state,
one
component,
Ph,
remains
bound.
Further,
can
each
other
with
presumptive
enhancers
state
and,
like
may
act
tethering
between
promoters
enhancers.
Overall,
our
data
suggest
for
loci
both
OFF
states.
Communications Biology,
Journal Year:
2023,
Volume and Issue:
6(1)
Published: April 20, 2023
Topologically
associating
domain
(TAD)
boundaries
partition
the
genome
into
distinct
regulatory
territories.
Anecdotal
evidence
suggests
that
their
disruption
may
interfere
with
normal
gene
expression
and
cause
disease
phenotypes1-3,
but
overall
extent
to
which
this
occurs
remains
unknown.
Here
we
demonstrate
targeted
deletions
of
TAD
a
range
disruptions
in
vivo
function
organismal
development.
We
used
CRISPR
editing
mice
individually
delete
eight
(11-80
kb
size)
from
genome.
All
examined
resulted
detectable
molecular
or
phenotypes,
included
altered
chromatin
interactions
expression,
reduced
viability,
anatomical
phenotypes.
observed
changes
local
3D
architecture
7
8
(88%)
cases,
including
merging
TADs
contact
frequencies
within
adjacent
deleted
boundary.
For
5
(63%)
loci
examined,
boundary
were
associated
increased
embryonic
lethality
other
developmental
example,
deletion
near
Smad3/Smad6
caused
complete
lethality,
while
Tbx5/Lhx5
severe
lung
malformation.
Our
findings
importance
sequences
for
reinforce
critical
need
carefully
consider
potential
pathogenicity
noncoding
affecting
clinical
genetics
screening.
Cell,
Journal Year:
2024,
Volume and Issue:
187(2), P. 331 - 344.e17
Published: Jan. 1, 2024
Enhancers
are
distal
DNA
elements
believed
to
loop
and
contact
promoters
control
gene
expression.
Recently,
we
found
diffraction-sized
transcriptional
condensates
at
genes
controlled
by
clusters
of
enhancers
(super-enhancers).
However,
a
direct
function
endogenous
in
controlling
expression
remains
elusive.
Here,
develop
live-cell
super-resolution
multi-color
3D-imaging
approaches
investigate
putative
roles
the
regulation
super-enhancer
Sox2.
In
contrast
enhancer
distance,
find
instead
that
condensate's
positional
dynamics
better
predictor
A
basal
bursting
occurs
when
condensate
is
far
(>1
μm),
but
burst
size
frequency
enhanced
moves
proximity
(<1
μm).
Perturbations
cohesin
local
do
not
prevent
affect
its
enhancement.
We
propose
three-way
kissing
model
whereby
interacts
transiently
with
locus
regulatory
bursting.
Nature Genetics,
Journal Year:
2024,
Volume and Issue:
56(4), P. 686 - 696
Published: March 11, 2024
Abstract
To
regulate
expression,
enhancers
must
come
in
proximity
to
their
target
gene.
However,
the
relationship
between
timing
of
enhancer–promoter
(E–P)
and
activity
remains
unclear,
with
examples
uncoupled,
anticorrelated
correlated
interactions.
assess
this,
we
selected
600
characterized
or
promoters
tissue-specific
Drosophila
embryos
performed
Capture-C
FACS-purified
myogenic
neurogenic
cells
during
specification
tissue
differentiation.
This
enabled
direct
comparison
E–P
transitioning
from
OFF-to-ON
ON-to-OFF
states
across
developmental
conditions.
showed
remarkably
similar
topologies
specified
muscle
neuronal
cells,
which
are
uncoupled
activity.
During
differentiation,
many
new
distal
interactions
emerge
where
changes
reflect
The
mode
regulation
therefore
appears
change
as
embryogenesis
proceeds,
largely
permissive
cell-fate
more
instructive
terminal
when
is
coupled
activation.
Nature Methods,
Journal Year:
2024,
Volume and Issue:
21(6), P. 983 - 993
Published: May 9, 2024
Abstract
The
inability
to
scalably
and
precisely
measure
the
activity
of
developmental
cis
-regulatory
elements
(CREs)
in
multicellular
systems
is
a
bottleneck
genomics.
Here
we
develop
dual
RNA
cassette
that
decouples
detection
quantification
tasks
inherent
multiplex
single-cell
reporter
assays.
resulting
measurement
expression
accurate
over
multiple
orders
magnitude,
with
precision
approaching
limit
set
by
Poisson
counting
noise.
Together
barcode
stabilization
via
circularization,
these
scalable
quantitative
reporters
provide
high-contrast
readouts,
analogous
classic
situ
assays
but
entirely
from
sequencing.
Screening
>200
regions
accessible
chromatin
vitro
model
early
mammalian
development,
identify
13
(8
previously
uncharacterized)
autonomous
cell-type-specific
CREs.
We
further
demonstrate
chimeric
CRE
pairs
generate
cognate
two-cell-type
profiles
assess
gain-
loss-of-function
phenotypes
variants
perturbed
transcription
factor
binding
sites.
Single-cell
can
be
applied
quantitatively
characterize
native,
synthetic
CREs
at
scale,
high
sensitivity
resolution.
Molecular Cell,
Journal Year:
2024,
Volume and Issue:
84(3), P. 415 - 428
Published: Jan. 18, 2024
Nearly
7
decades
have
elapsed
since
Francis
Crick
introduced
the
central
dogma
of
molecular
biology,
as
part
his
ideas
on
protein
synthesis,
setting
fundamental
rules
sequence
information
transfer
from
DNA
to
RNAs
and
proteins.
We
learned
that
gene
expression
is
finely
tuned
in
time
space,
due
activities
proteins
regulatory
elements,
through
cell-type-specific
three-dimensional
conformations
genome.
Here,
we
review
major
advances
genome
biology
discuss
a
set
regulation
highlight
how
various
biomolecular
assemblies
lead
formation
structural
features
within
nucleus,
with
roles
transcriptional
control.
conclude
by
suggesting
further
developments
will
help
capture
complex,
dynamic,
often
spatially
restricted
events
govern
mammalian
cells.
