bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 10, 2024
Abstract
Lamina-associated
domains
(LADs)
are
megabase-sized
genomic
regions
that
interact
with
the
nuclear
lamina
(NL).
It
is
not
yet
understood
how
their
interactions
NL
encoded
in
DNA.
Here,
we
designed
an
efficient
LAD
“scrambling”
approach,
based
on
transposon-mediated
local
hopping
of
loxP
recombination
sites,
to
generate
series
large
deletions
and
inversions
span
LADs
flanking
sequences.
Mapping
these
rearrangements
revealed
a
single
contacts
through
multiple
act
cooperatively
or
redundantly;
some
have
more
affinity
for
than
others
can
pull
neighbouring
sequences
NL.
Genes
drawn
towards
showed
often,
but
always,
reduced
expression
increased
H3K9me3
levels.
Furthermore,
when
placed
close
enough
each
other.
These
results
elucidate
principles
govern
positioning
inside
cell
nucleus.
Highlights
Efficient
generation
by
transposon
elements.
multivalent,
subregions
being
potent
tethers
others.
cooperate
promote
association
Changes
often
accompanied
changes
gene
activity
H3K9me3.
Epigenetics & Chromatin,
Год журнала:
2023,
Номер
16(1)
Опубликована: Май 30, 2023
Abstract
Background
Interactions
among
topologically
associating
domains
(TADs),
and
between
the
nuclear
envelope
(NE)
lamina-associated
(LADs)
are
expected
to
shape
various
aspects
of
three-dimensional
(3D)
chromatin
structure
dynamics;
however,
relevant
genome-wide
experiments
that
may
provide
statistically
significant
conclusions
remain
difficult.
Results
We
have
developed
a
coarse-grained
dynamical
model
D.
melanogaster
nuclei
at
TAD
resolution
explicitly
accounts
for
four
distinct
epigenetic
classes
TADs
LAD–NE
interactions.
The
is
parameterized
reproduce
experimental
Hi-C
map
wild
type
(WT)
nuclei;
it
describes
time
evolution
over
G1
phase
interphase.
simulations
include
an
ensemble
nuclei,
corresponding
experimentally
observed
set
several
possible
mutual
arrangements
chromosomal
arms.
validated
against
multiple
structural
features
from
different
not
used
in
development.
Predicted
positioning
all
LADs
NE
highly
dynamic—the
same
LAD
can
attach,
detach
move
far
away
times
during
probabilities
be
contact
with
vary
by
order
magnitude,
despite
having
affinity
model.
These
mostly
determined
variable
local
linear
density
along
genome,
which
also
has
strong
effect
on
predicted
individual
--
higher
probability
near
largely
surrounding
this
TAD.
distribution
chromosome
chains
plays
notable
role
maintaining
non-random
average
global
chromatin.
Relatively
high
WT
substantially
reduces
sensitivity
radial
variations
strength
TAD–TAD
interactions
compared
lamin
depleted
where
small
(0.5
kT
)
increase
cross-type
doubles
central
nucleus
region.
Conclusions
A
entire
fruit
fly
genome
makes
predictions
biological
interest.
affects
their
mobile
TADs,
playing
creating
conjecture
important
attractive
stabilize
inevitable
cell-to-cell
Cells,
Год журнала:
2023,
Номер
12(6), С. 932 - 932
Опубликована: Март 18, 2023
The
Linker
of
Nucleoskeleton
and
Cytoskeleton
(LINC)
complex
transduces
nuclear
mechanical
inputs
suggested
to
control
chromatin
organization
gene
expression;
however,
the
underlying
mechanism
is
currently
unclear.
We
show
here
that
LINC
needed
minimize
repression
in
muscle
tissue,
where
nuclei
are
exposed
significant
during
contraction.
To
this
end,
genomic
binding
profiles
Polycomb,
Heterochromatin
Protein1
(HP1a)
repressors,
RNA-Pol
II
were
studied
Drosophila
larval
muscles
lacking
functional
complex.
A
increase
Polycomb
parallel
reduction
RNA-Pol-II
a
set
genes
was
observed.
Consistently,
enhanced
tri-methylated
H3K9
H3K27
repressive
modifications
reduced
activation
by
acetylation
found.
Furthermore,
larger
H3K27me3
clusters,
redistribution
from
periphery
towards
center,
detected
live
mutant
muscles.
Computer
simulation
indicated
observed
dissociation
envelope
promotes
growth
clusters.
Thus,
we
suggest
promoting
chromatin–nuclear
binding,
restricts
size
thereby
limiting
transcription
repressor,
directing
robust
fibers.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 10, 2024
Abstract
Lamina-associated
domains
(LADs)
are
megabase-sized
genomic
regions
that
interact
with
the
nuclear
lamina
(NL).
It
is
not
yet
understood
how
their
interactions
NL
encoded
in
DNA.
Here,
we
designed
an
efficient
LAD
“scrambling”
approach,
based
on
transposon-mediated
local
hopping
of
loxP
recombination
sites,
to
generate
series
large
deletions
and
inversions
span
LADs
flanking
sequences.
Mapping
these
rearrangements
revealed
a
single
contacts
through
multiple
act
cooperatively
or
redundantly;
some
have
more
affinity
for
than
others
can
pull
neighbouring
sequences
NL.
Genes
drawn
towards
showed
often,
but
always,
reduced
expression
increased
H3K9me3
levels.
Furthermore,
when
placed
close
enough
each
other.
These
results
elucidate
principles
govern
positioning
inside
cell
nucleus.
Highlights
Efficient
generation
by
transposon
elements.
multivalent,
subregions
being
potent
tethers
others.
cooperate
promote
association
Changes
often
accompanied
changes
gene
activity
H3K9me3.
