bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июль 14, 2022
Abstract
The
massive
accumulation
of
extrachromosomal
ribosomal
DNA
circles
(ERCs)
in
yeast
mother
cells
has
been
long
cited
as
the
primary
driver
replicative
ageing.
ERCs
arise
through
(rDNA)
recombination
and
a
wealth
genetic
data
connects
rDNA
instability
events
giving
rise
to
with
shortened
lifespan
other
ageing
pathologies.
However,
we
understand
little
about
molecular
effects
ERC
accumulation.
Here
studied
presence
absence
ERCs,
unexpectedly
found
no
evidence
gene
expression
differences
that
might
indicate
stress
responses
or
metabolic
feedback
caused
by
ERCs.
Neither
did
observe
any
global
change
widespread
disruption
accompanies
ageing,
altogether
suggesting
are
largely
inert.
Much
differential
was
actually
associated
markers
Senescence
Entry
Point
(SEP),
showing
senescence
rather
than
age
underlies
these
changes.
Cells
passed
SEP
irrespective
but
be
copy
number
amplification
region
chromosome
XII
between
telomere
(ChrXIIr),
which
arises
aged
due
different
mechanism
Therefore,
although
increases
dramatically
accumulation,
our
findings
implicate
ChrXIIr,
during
budding
The Journal of Cell Biology,
Год журнала:
2024,
Номер
223(4)
Опубликована: Фев. 20, 2024
DNA
methylation
(DNAme)
is
a
key
epigenetic
mark
that
regulates
critical
biological
processes
maintaining
overall
genome
stability.
Given
its
pleiotropic
function,
studies
of
DNAme
dynamics
are
crucial,
but
currently
available
tools
to
interfere
with
have
limitations
and
major
cytotoxic
side
effects.
Here,
we
present
cell
models
allow
inducible
reversible
modulation
through
DNMT1
depletion.
By
dynamically
assessing
whole
locus-specific
effects
induced
passive
demethylation
divisions,
reveal
cooperative
activity
between
DNMT3B,
not
DNMT3A,
maintain
control
DNAme.
We
show
gradual
loss
accompanied
by
progressive
changes
in
heterochromatin,
compartmentalization,
peripheral
localization.
coincides
reduction
fitness
due
G1
arrest,
minor
levels
mitotic
failure.
Altogether,
this
system
allows
DNMTs
fine
temporal
resolution,
which
may
help
the
etiologic
link
dysfunction
human
disease.
Recent
advances
chromatin
capture,
imaging
techniques,
and
polymer
modeling
have
dramatically
enhanced
quantitative
understanding
of
chromosomal
folding.
However,
the
dynamism
inherent
in
genome
architectures
due
to
physical
biochemical
forces
their
impact
on
nuclear
architecture
cellular
functions
remains
elusive.
While
four
dimensions
is
becoming
more
common,
there
a
conspicuous
lack
physics-based
computational
tools
appropriate
for
revealing
that
shape
dynamics.
To
this
end,
we
developed
multiphase
liquid
model
nucleus,
which
can
resolve
territories,
compartments,
lamina
using
data-informed
free-energy
function.
The
enables
rapid
hypothesis-driven
prototyping
dynamics
dimensions,
thereby
facilitating
comparison
with
whole
nucleus
experiments.
As
an
application,
map
phase
diagram
various
possible
morphologies.
We
shed
light
interplay
adhesive
cohesive
interactions
give
rise
distinct
radial
organization
seen
conventional,
inverted,
senescent
architectures.
results
also
show
highly
dynamic
nature
organization,
disruption
leads
significant
variability
domain
coarsening
consequently
architecture.
highlights
oblate
geometry
heterochromatin-subtype
global
local
asymmetry
compartments.
Published
by
American
Physical
Society
2024
Epigenomes,
Год журнала:
2025,
Номер
9(2), С. 11 - 11
Опубликована: Апрель 12, 2025
DNA
methylation
is
an
important
epigenetic
modification
with
a
plethora
of
effects
on
cells,
ranging
from
the
regulation
gene
transcription
to
shaping
chromatin
structure.
Notably,
occurs
thanks
activity
methyltransferases
(DNMTs),
which
covalently
add
methyl
group
cytosine
in
position
5′
CpG
dinucleotides.
Different
strategies
have
been
developed
study
involving
either
DNMTs
inhibition
(passive
demethylation)
or
use
Ten-eleven
translocation
protein
(TET)
family
enzymes,
directly
demethylate
(active
demethylation).
In
this
manuscript,
we
will
briefly
cover
most
commonly
used
last
two
decades
achieve
demethylation,
along
their
cells.
We
also
discuss
some
newest
inducible
ways
inhibit
without
remarkable
side
effects,
as
well
effect
non-coding
RNAs
methylation.
Lastly,
examine
biomedical
research.
PLoS Biology,
Год журнала:
2023,
Номер
21(8), С. e3002250 - e3002250
Опубликована: Авг. 29, 2023
The
massive
accumulation
of
extrachromosomal
ribosomal
DNA
circles
(ERCs)
in
yeast
mother
cells
has
been
long
cited
as
the
primary
driver
replicative
ageing.
ERCs
arise
through
(rDNA)
recombination,
and
a
wealth
genetic
data
connects
rDNA
instability
events
giving
rise
to
with
shortened
life
span
other
ageing
pathologies.
However,
we
understand
little
about
molecular
effects
ERC
accumulation.
Here,
studied
presence
absence
ERCs,
unexpectedly
found
no
evidence
gene
expression
differences
that
might
indicate
stress
responses
or
metabolic
feedback
caused
by
ERCs.
Neither
did
observe
any
global
change
widespread
disruption
accompanies
ageing,
altogether
suggesting
are
largely
inert.
Much
differential
was
actually
associated
markers
senescence
entry
point
(SEP),
showing
senescence,
rather
than
age,
underlies
these
changes.
Cells
passed
SEP
irrespective
but
be
copy
number
amplification
region
chromosome
XII
between
telomere
(ChrXIIr)
forming
linear
fragments
up
approximately
1.8
Mb
size,
which
aged
due
different
mechanism
Therefore,
although
increases
dramatically
age
accumulation,
our
findings
implicate
ChrXIIr,
during
budding
Abstract
Background
The
nuclear
lamina
links
the
membrane
to
chromosomes
and
plays
a
crucial
role
in
regulating
chromatin
states
gene
expression.
However,
current
knowledge
of
plants
is
limited
compared
animals
humans.
Results
This
study
mainly
focused
on
elucidating
mechanism
through
which
putative
component
protein
KAKU4
regulates
expression
Arabidopsis
leaves.
Thus,
we
constructed
network
using
association
proteins
lamin-like
proteins,
revealing
that
strongly
associated
with
or
epigenetic
modifiers.
Then,
conducted
ChIP-seq
technology
generate
global
epigenomic
profiles
H3K4me3,
H3K27me3,
H3K9me2
leaves
for
mutant
(
kaku4-2
)
wild-type
(WT)
alongside
RNA-seq
method
profiles.
comprehensive
state-based
analyses
indicate
knockdown
has
strongest
effect
followed
by
H3K9me2,
least
impact
leading
significant
changes
genome.
We
discovered
caused
transition
between
two
types
repressive
epigenetics
marks,
some
specific
PLAD
regions.
combination
transcriptomic
data
WT
suggested
may
regulate
key
biological
processes,
such
as
programmed
cell
death
hormone
signaling
pathways,
affecting
H3K27me3
modification
Conclusions
In
summary,
our
results
indicated
directly
and/or
indirectly
chromatin/epigenetic
modifiers
demonstrated
essential
roles
states,
transcriptional
regulation,
diverse
processes
.
Cellular and Molecular Life Sciences,
Год журнала:
2024,
Номер
82(1)
Опубликована: Дек. 18, 2024
Methylation
of
cytosine
in
CpG
dinucleotides
is
an
epigenetic
modification
carried
out
by
DNA-methyltransferases
(DNMTs)
that
contributes
to
chromatin
condensation
and
structure
and,
thus,
gene
transcription
regulation
chromosome
stability.
DNMT1
maintains
the
DNA
methylation
pattern
genome
at
each
cell
cycle
copying
it
newly
synthesized
strand
during
S-phase.
pharmacological
inhibition
as
well
genetic
knockout
knockdown,
leads
passive
loss.
However,
these
strategies
have
been
associated
with
different
fates,
even
same
background,
suggesting
they
can
question
interpretation
obtained
results.
Using
a
system
which
endogenous
fused
inducible
degron
be
rapidly
degraded,
we
found
non-tumoral
RPE-1
cells,
loss
progressively
induced
proliferation
slowing-down
arrest
G1/S
transition.
The
latter
due
p21
activation,
partly
mediated
p53
global
reduction
methylation.
restoration
rescues
proliferation,
indicating
its
deregulation
sensed
tunable
cellular
stress.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 9, 2023
ABSTRACT
DNA
methylation
(DNAme)
is
a
key
epigenetic
mark
that
regulates
critical
biological
processes
maintaining
overall
genome
stability.
Given
its
pleiotropic
function,
studies
of
DNAme
dynamics
are
crucial,
but
currently
available
tools
to
interfere
with
have
limitations
and
major
cytotoxic
side
effects.
Here,
we
present
untransformed
cancer
cell
models
allow
inducible
reversible
global
modulation
through
DNMT1
depletion.
By
dynamically
assessing
the
effects
induced
passive
demethylation
divisions
at
both
whole
locus-specific
level,
reveal
cooperative
activity
between
DNMT3B
maintain
control
DNAme.
Moreover,
show
gradual
loss
accompanied
by
progressive
changes
in
heterochromatin
abundance,
compartmentalization,
peripheral
localization.
coincided
reduction
fitness
due
G1
arrest,
minor
level
mitotic
failure.
Altogether,
this
powerful
system
allows
DNMT
fine
temporal
resolution,
which
may
help
etiologic
link
dysfunction
human
disease.
Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Сен. 13, 2024
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Frontotemporal
Dementia
(FTD),
and
Amyotrophic
lateral
sclerosis
(ALS)
are
complex
fatal
neurodegenerative
diseases.
While
current
treatments
for
these
diseases
do
alleviate
some
symptoms,
there
is
an
imperative
need
novel
able
to
stop
their
progression.
For
all
of
ailments,
most
cases
occur
sporadically
have
no
known
genetic
cause.
Only
a
small
percentage
patients
bear
mutations
which
in
multitude
genes.
Hence,
it
clear
that
factors
alone
not
explain
occurrence.
Chromatin,
DNA-histone
whose
basic
unit
the
nucleosome,
divided
into
euchromatin,
open
form
accessible
transcriptional
machinery,
heterochromatin,
closed
transcriptionally
inactive.
Protruding
out
histone
tails
undergo
post-translational
modifications
(PTMs)
including
methylation,
acetylation,
phosphorylation
at
specific
residues
connected
different
chromatin
structural
states
regulate
access
machinery.
Epigenetic
mechanisms,
PTMs
changes
structure,
could
help
processes
illuminate
treatment
targets.
Recent
research
has
revealed
heterochromatin
loss
or
gain
neurodegeneration.
Here,
we
review
evidence
epigenetic
occurring
AD,
PD,
FTD/ALS.
We
focus
specifically
on
alterations
landscape,
expression
modifying
enzymes
remodelers
as
well
consequences
structure.
also
highlight
potential
therapies
treatment.
Given
reversibility
pharmacological
accessibility,
mechanisms
provide
promising
avenue
treatments.
Altogether,
findings
underscore
thorough
characterization
structure
