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.
Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Янв. 9, 2018
Despite
an
abundance
of
new
studies
about
topologically
associating
domains
(TADs),
the
role
genetic
information
in
TAD
formation
is
still
not
fully
understood.
Here
we
use
our
software,
HiCExplorer
(hicexplorer.readthedocs.io)
to
annotate
>2800
high-resolution
(570
bp)
boundaries
Drosophila
melanogaster.
We
identify
eight
DNA
motifs
enriched
at
boundaries,
including
a
motif
bound
by
M1BP
protein,
and
two
boundary
motifs.
In
contrast
mammals,
CTCF
only
on
small
fraction
flanking
inactive
chromatin
while
most
active
contain
or
Beaf-32
proteins.
demonstrate
that
can
be
accurately
predicted
using
sequences
open
sites.
propose
sequence
guides
genome
architecture
allocation
proteins
genome.
Finally,
present
interactive
online
database
access
explore
spatial
organization
fly,
mouse
human
genomes,
available
http://chorogenome.ie-freiburg.mpg.de
.
Science,
Год журнала:
2019,
Номер
366(6471), С. 1338 - 1345
Опубликована: Ноя. 22, 2019
Eukaryotic
genomes
are
folded
into
loops
and
topologically
associating
domains,
which
contribute
to
chromatin
structure,
gene
regulation,
recombination.
These
structures
depend
on
cohesin,
a
ring-shaped
DNA-entrapping
adenosine
triphosphatase
(ATPase)
complex
that
has
been
proposed
form
by
extrusion.
Such
an
activity
observed
for
condensin,
forms
in
mitosis,
but
not
cohesin.
Using
biochemical
reconstitution,
we
found
single
human
cohesin
complexes
DNA
symmetrically
at
rates
up
2.1
kilo-base
pairs
per
second.
Loop
formation
maintenance
cohesin's
ATPase
NIPBL-MAU2,
topological
entrapment
of
During
loop
formation,
NIPBL-MAU2
reside
the
base
loops,
indicates
they
generate
Our
results
show
active
holoenzyme
interacts
with
either
pseudo-topologically
or
non-topologically
extrude
genomic
interphase
loops.
Cell,
Год журнала:
2017,
Номер
169(4), С. 693 - 707.e14
Опубликована: Май 1, 2017
The
spatial
organization
of
chromosomes
influences
many
nuclear
processes
including
gene
expression.
cohesin
complex
shapes
the
3D
genome
by
looping
together
CTCF
sites
along
chromosomes.
We
show
here
that
chromatin
loop
size
can
be
increased
and
duration
with
which
embraces
DNA
determines
degree
to
loops
are
enlarged.
Cohesin's
release
factor
WAPL
restricts
this
extension
also
prevents
between
incorrectly
oriented
sites.
reveal
SCC2/SCC4
promotes
formation
topologically
associated
domains
(TADs).
Our
data
support
model
structures
through
processive
enlargement
TADs
reflect
polyclonal
collections
in
making.
Finally,
we
find
whereas
chromosomal
looping,
it
rather
limits
compartmentalization.
conclude
balanced
activity
enables
correctly
structure
Tracking
mitotic
chromosome
formation
How
cells
pack
DNA
into
fully
compact,
rod-shaped
chromosomes
during
mitosis
has
fascinated
cell
biologists
for
more
than
a
century.
Gibcus
et
al.
delineated
the
conformational
transition
trajectory
from
interphase
chromatin
to
minute
by
cycle.
The
is
organized
in
spiral
staircase
architecture
which
loops
emanate
radially
centrally
located
helical
scaffold.
molecular
machines
condensin
I
and
II
play
distinct
roles
these
processes:
Condensin
essential
winding,
whereas
modulates
organization
within
each
turn.
Science
,
this
issue
p.
eaao6135
