Folding
of
mammalian
genomes
into
spatial
domains
is
critical
for
gene
regulation.
The
insulator
protein
CTCF
and
cohesin
control
domain
location
by
folding
loop
structures,
which
are
widely
thought
to
be
stable.
Combining
genomic
biochemical
approaches
we
show
that
co-occupy
the
same
sites
physically
interact
as
a
biochemically
stable
complex.
However,
using
single-molecule
imaging
find
binds
chromatin
much
more
dynamically
than
(~1–2
min
vs.
~22
residence
time).
Moreover,
after
unbinding,
quickly
rebinds
another
cognate
site
unlike
search
process
long
(~1
~33
min).
Thus,
form
rapidly
exchanging
'dynamic
complex'
rather
typical
Since
required
formation,
our
results
suggest
loops
dynamic
frequently
break
reform
throughout
cell
cycle.
Genome biology,
Journal Year:
2018,
Volume and Issue:
19(1)
Published: Aug. 24, 2018
We
present
HiGlass,
an
open
source
visualization
tool
built
on
web
technologies
that
provides
a
rich
interface
for
rapid,
multiplex,
and
multiscale
navigation
of
2D
genomic
maps
alongside
1D
tracks,
allowing
users
to
combine
various
data
types,
synchronize
multiple
modalities,
share
fully
customizable
views
with
others.
demonstrate
its
utility
in
exploring
different
experimental
conditions,
comparing
the
results
analyses,
creating
interactive
snapshots
collaborators
broader
public.
HiGlass
is
accessible
online
at
http://higlass.io
also
available
as
containerized
application
can
be
run
any
platform.
Cell,
Journal Year:
2017,
Volume and Issue:
171(3), P. 557 - 572.e24
Published: Oct. 1, 2017
Chromosome
conformation
capture
technologies
have
revealed
important
insights
into
genome
folding.
Yet,
how
spatial
architecture
is
related
to
gene
expression
and
cell
fate
remains
unclear.
We
comprehensively
mapped
3D
chromatin
organization
during
mouse
neural
differentiation
in
vitro
vivo,
generating
the
highest-resolution
Hi-C
maps
available
date.
found
that
transcription
correlated
with
insulation
long-range
interactions,
but
dCas9-mediated
activation
insufficient
for
creating
TAD
boundaries
de
novo.
Additionally,
we
discovered
contacts
between
bodies
of
exon-rich,
active
genes
all
types.
During
differentiation,
TADs
become
less
pronounced
while
inactive
interact
more
strongly.
An
extensive
Polycomb
network
stem
cells
disrupted,
dynamic
interactions
factors
appear
vivo.
Finally,
type-specific
enhancer-promoter
are
established
concomitant
expression.
This
work
shows
multiple
influence
dynamics
development.
Science,
Journal Year:
2018,
Volume and Issue:
362(6413)
Published: Oct. 26, 2018
The
spatial
organization
of
chromatin
is
pivotal
for
regulating
genome
functions.
We
report
an
imaging
method
tracing
with
kilobase-
and
nanometer-scale
resolution,
unveiling
conformation
across
topologically
associating
domains
(TADs)
in
thousands
individual
cells.
Our
data
revealed
TAD-like
structures
globular
sharp
domain
boundaries
single
varied
from
cell
to
cell,
occurring
nonzero
probabilities
at
all
genomic
positions
but
preferentially
CCCTC-binding
factor
(CTCF)-
cohesin-binding
sites.
Notably,
cohesin
depletion,
which
abolished
TADs
the
population-average
level,
did
not
diminish
cells
eliminated
preferential
boundary
positions.
Moreover,
we
observed
widespread,
cooperative,
multiway
interactions,
remained
after
depletion.
These
results
provide
critical
insight
into
mechanisms
underlying
hub
formation.
