Nuclear basket proteins Mlp1 and Nup2 drive heat shock-induced 3D genome restructuring
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 2, 2025
ABSTRACT
The
nuclear
pore
complex
(NPC),
a
multisubunit
located
within
the
envelope,
regulates
RNA
export
and
import
of
proteins.
Here
we
address
role
NPC
in
driving
thermal
stress-induced
3D
genome
repositioning
Heat
Shock
Responsive
(
HSR
)
genes
yeast.
We
found
that
two
basket
proteins,
Mlp1
Nup2,
although
dispensable
for
integrity,
are
required
into
coalesced
chromatin
clusters,
consistent
with
their
strong,
heat
shock-dependent
recruitment
to
gene
regulatory
coding
regions.
clustering
occurs
predominantly
nucleoplasm
is
independent
essential
scaffold-associated
proteins
Nup1
Nup145.
Notably,
double
depletion
Nup2
has
little
effect
on
formation
Factor
1
(Hsf1)-containing
transcriptional
condensates,
Hsf1
Pol
II
genes,
or
mRNA
abundance.
Our
results
define
restructuring
extrinsic
downstream
activation.
Язык: Английский
Nuclear Basket Proteins Mlp1 and Nup2 Drive Heat Shock–Induced 3D Genome Restructuring
Опубликована: Янв. 31, 2025
The
nuclear
pore
complex
(NPC),
a
multisubunit
located
within
the
envelope,
regulates
RNA
export
and
import
of
proteins.
Here
we
address
role
NPC
in
driving
thermal
stress-induced
3D
genome
repositioning
_Heat
Shock
Responsive_
(_HSR_)
genes
yeast.
We
found
that
two
basket
proteins,
Mlp1
Nup2,
although
dispensable
for
integrity,
are
required
_HSR_
into
coalesced
chromatin
clusters,
consistent
with
their
strong,
heat
shock-dependent
recruitment
to
gene
regulatory
coding
regions.
clustering
occurs
predominantly
nucleoplasm
is
independent
essential
scaffold-associated
proteins
Nup1
Nup145.
Notably,
double
depletion
Nup2
has
little
effect
on
formation
Heat
Factor
1
(Hsf1)-containing
transcriptional
condensates,
Hsf1
Pol
II
genes,
or
mRNA
abundance.
Our
results
define
restructuring
extrinsic
downstream
activation.
Язык: Английский
Heat Shock Factor 1 forms nuclear condensates and restructures the yeast genome before activating target genes
eLife,
Год журнала:
2024,
Номер
12
Опубликована: Окт. 15, 2024
In
insects
and
mammals,
3D
genome
topology
has
been
linked
to
transcriptional
states
yet
whether
this
link
holds
for
other
eukaryotes
is
unclear.
Using
both
ligation
proximity
fluorescence
microscopy
assays,
we
show
that
in
Saccharomyces
cerevisiae
,
Heat
Shock
Response
(
HSR
)
genes
dispersed
across
multiple
chromosomes
under
the
control
of
Factor
(Hsf1)
rapidly
reposition
cells
exposed
acute
ethanol
stress
engage
concerted,
Hsf1-dependent
intergenic
interactions.
Accompanying
reconfiguration
equally
rapid
formation
Hsf1-containing
condensates.
However,
contrast
transience
Hsf1-driven
interactions
peak
within
10–20
min
dissipate
1
hr
presence
8.5%
(v/v)
ethanol,
condensates
are
stably
maintained
hours.
Moreover,
same
conditions,
Pol
II
occupancy
genes,
chromatin
remodeling,
RNA
expression
detectable
only
later
response
much
(>1
hr).
This
contrasts
with
coordinate
thermal
(39°C)
where
occupancy,
transcription,
histone
eviction,
interactions,
Hsf1
all
transient
(peak
2.5–10
Therefore,
forms
condensates,
restructures
transcriptionally
activates
proteotoxic
but
does
so
strikingly
different
kinetics.
subjected
stress,
repositions
target
before
activating
them.
Язык: Английский
Heat Shock Factor 1 forms nuclear condensates and restructures the yeast genome before activating target genes
eLife,
Год журнала:
2023,
Номер
12
Опубликована: Ноя. 22, 2023
In
insects
and
mammals,
3D
genome
topology
has
been
linked
to
transcriptional
states
yet
whether
this
link
holds
for
other
eukaryotes
is
unclear.
Using
both
ligation
proximity
fluorescence
microscopy
assays,
we
show
that
in
Saccharomyces
cerevisiae
,
Heat
Shock
Response
(
HSR
)
genes
dispersed
across
multiple
chromosomes
under
the
control
of
Factor
(Hsf1)
rapidly
reposition
cells
exposed
acute
ethanol
stress
engage
concerted,
Hsf1-dependent
intergenic
interactions.
Accompanying
reconfiguration
equally
rapid
formation
Hsf1-containing
condensates.
However,
contrast
transience
Hsf1-driven
interactions
peak
within
10–20
min
dissipate
1
hr
presence
8.5%
(v/v)
ethanol,
condensates
are
stably
maintained
hours.
Moreover,
same
conditions,
Pol
II
occupancy
genes,
chromatin
remodeling,
RNA
expression
detectable
only
later
response
much
(>1
hr).
This
contrasts
with
coordinate
thermal
(39°C)
where
occupancy,
transcription,
histone
eviction,
interactions,
Hsf1
all
transient
(peak
2.5–10
Therefore,
forms
condensates,
restructures
transcriptionally
activates
proteotoxic
but
does
so
strikingly
different
kinetics.
subjected
stress,
repositions
target
before
activating
them.
Язык: Английский