Proceedings of the National Academy of Sciences,
Год журнала:
2022,
Номер
119(32)
Опубликована: Авг. 1, 2022
The
eukaryotic
genome
is
partitioned
into
distinct
topological
domains
separated
by
boundary
elements.
Emerging
data
support
the
concept
that
several
well-established
nuclear
compartments
are
ribonucleoprotein
condensates
assembled
through
physical
process
of
phase
separation.
Here,
based
on
our
demonstration
chemical
disruption
condensate
assembly
weakens
insulation
properties
a
specific
subset
(∼20%)
topologically
associated
domain
(TAD)
boundaries,
we
report
disrupted
boundaries
characterized
high
level
transcription
and
striking
spatial
clustering.
These
regions
tend
to
be
spatially
associated,
even
interchromosomally,
segregate
with
speckles,
harbor
“housekeeping”
genes
widely
expressed
in
diverse
cell
types.
observations
reveal
previously
unappreciated
mode
organization
mediated
conserved
elements
harboring
highly
units
transcriptional
condensates.
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2021,
Номер
14(2), С. a040683 - a040683
Опубликована: Июнь 14, 2021
Karsten
Rippe
Division
of
Chromatin
Networks,
German
Cancer
Research
Center
(DKFZ)
and
Bioquant,
69120
Heidelberg,
Germany
Correspondence:
Karsten.Rippe{at}dkfz.de
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Фев. 16, 2024
Whether
phase-separation
is
involved
in
the
organization
of
transcriptional
machinery
and
if
it
aids
or
inhibits
process
a
matter
intense
debate.
In
this
Mini
Review,
we
will
cover
current
knowledge
regarding
role
condensates
on
gene
expression
regulation.
We
summarize
latest
discoveries
relationship
between
condensate
formation,
genome
organization,
activity,
focusing
strengths
weaknesses
experimental
approaches
used
to
interrogate
these
aspects
transcription
living
cells.
Finally,
discuss
challenges
for
future
research.
Nuclear
compartments
are
membrane-less
regions
enriched
in
functionally
related
molecules.
RNA
is
a
major
component
of
many
nuclear
compartments,
but
the
identity
and
dynamics
transcripts
within
poorly
understood.
Here,
we
applied
reverse
transcribe
tagment
(RT&Tag)
to
human
cell
lines
identify
transcript
populations
Polycomb
domains
speckles.
We
also
developed
SLAM-RT&Tag,
which
combines
metabolic
labeling
with
RT&Tag,
quantify
compartments.
observed
unique
differing
structures
each
compartment.
Intriguingly,
exceptionally
long
genes
transcribed
adjacent
transiently
associated
chromatin.
By
contrast,
speckles
act
as
quality
control
checkpoints
that
confine
incompletely
spliced
polyadenylated
facilitate
their
post-transcriptional
splicing.
In
summary,
demonstrate
at
undergo
distinct
processing
mechanisms,
highlighting
pivotal
role
compartmentalization
maturation.
Journal of Cell Science,
Год журнала:
2022,
Номер
135(13)
Опубликована: Июль 1, 2022
Nuclear
speckles
are
dynamic
membraneless
bodies
located
in
the
cell
nucleus.
They
harbor
RNAs
and
proteins,
many
of
which
splicing
factors,
that
together
display
complex
biophysical
properties
dictating
nuclear
speckle
formation
maintenance.
Although
these
were
discovered
decades
ago,
only
recently
has
in-depth
genomic
analysis
begun
to
unravel
their
essential
functions
modulation
gene
activity.
Major
advancements
mapping
techniques
combined
with
microscopy
approaches
have
enabled
insights
into
roles
may
play
enhancing
expression,
how
positioning
specific
landmarks
can
regulate
expression
RNA
processing.
Some
studies
drawn
a
link
between
disease.
Certain
maladies
either
involve
directly
or
dictate
localization
reorganization
factors.
This
is
most
striking
during
viral
infection,
as
viruses
alter
entire
architecture
highjack
host
machinery.
As
discussed
this
Review,
represent
fascinating
target
study
not
reveal
links
positioning,
genome
subcompartments
activity,
but
also
potential
for
therapeutics.
Cell Reports,
Год журнала:
2023,
Номер
42(6), С. 112567 - 112567
Опубликована: Май 26, 2023
Chromatin
compaction
differences
may
have
a
strong
impact
on
accessibility
of
individual
macromolecules
and
macromolecular
assemblies
to
their
DNA
target
sites.
Estimates
based
fluorescence
microscopy
with
conventional
resolution,
however,
suggest
only
modest
(∼2-10×)
between
the
active
nuclear
compartment
(ANC)
inactive
(INC).
Here,
we
present
maps
landscapes
true-to-scale
densities,
ranging
from
<5
>300
Mbp/μm3.
Maps
are
generated
human
mouse
cell
nuclei
single-molecule
localization
at
∼20
nm
lateral
∼100
axial
optical
resolution
supplemented
by
electron
spectroscopic
imaging.
Microinjection
fluorescent
nanobeads
sizes
corresponding
for
transcription
into
living
cells
demonstrates
movements
within
ANC
exclusion
INC.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 9, 2023
The
mammalian
nucleus
is
compartmentalized
by
diverse
subnuclear
structures.
These
structures,
marked
nuclear
bodies
and
histone
modifications,
are
often
cell-type
specific
affect
gene
regulation
3D
genome
organization
Annual Review of Biophysics,
Год журнала:
2024,
Номер
53(1), С. 221 - 245
Опубликована: Фев. 12, 2024
Chromatin
organization
plays
a
critical
role
in
cellular
function
by
regulating
access
to
genetic
information.
However,
understanding
chromatin
folding
is
challenging
due
its
complex,
multiscale
nature.
Significant
progress
has
been
made
studying
vitro
systems,
uncovering
the
structure
of
individual
nucleosomes
and
their
arrays,
elucidating
physicochemical
forces
stabilizing
these
structures.
Additionally,
remarkable
advancements
have
achieved
characterizing
vivo,
particularly
at
whole-chromosome
level,
revealing
important
features
such
as
loops,
topologically
associating
domains,
nuclear
compartments.
bridging
gap
between
vivo
studies
remains
challenging.
The
resemblance
conformations
relevance
internucleosomal
interactions
for
are
subjects
debate.
This
article
reviews
experimental
computational
conducted
various
length
scales,
highlighting
significance
intrinsic
roles
vivo.
In
eukaryotes,
DNA-associated
protein
complexes
coevolve
with
genomic
sequences
to
orchestrate
chromatin
folding.
We
investigate
the
relationship
between
DNA
sequence
and
spontaneous
loading
activity
of
components
in
absence
coevolution.
Using
bacterial
genomes
integrated
into
Saccharomyces
cerevisiae
,
which
diverged
from
yeast
more
than
2
billion
years
ago,
we
show
that
nucleosomes,
cohesins,
associated
transcriptional
machinery
can
lead
formation
two
different
archetypes,
one
transcribed
other
silent,
independently
heterochromatin
formation.
These
archetypes
also
form
on
eukaryotic
exogenous
sequences,
depend
composition,
be
predicted
using
neural
networks
trained
native
genome.
They
do
not
mix
nucleus,
leading
a
bipartite
nuclear
compartmentalization,
reminiscent
organization
vertebrate
nuclei.
