Nucleic Acids Research,
Год журнала:
2025,
Номер
53(3)
Опубликована: Янв. 24, 2025
Abstract
Chromatin
remodeling,
which
involves
the
histone-to-protamine
exchange
process
during
spermiogenesis,
is
crucial
for
sperm
nuclear
condensation
and
male
fertility.
However,
key
regulators
underlying
molecular
mechanisms
involved
in
this
remain
largely
unexplored.
In
study,
we
discovered
that
deficiency
family
with
sequence
similarity
170
member
A
(Fam170a)
led
to
abnormal
morphology
infertility
mice,
mirroring
observation
of
very
low
Fam170a
transcription
levels
infertile
men
teratozoospermia.
Further
investigation
revealed
plays
a
significant
role
chromatin
remodeling
process.
This
was
evidenced
by
earlier
core
histone
removal,
accelerated
translation
degradation
transition
proteins,
reduced
protamine
incorporation
spermiogenesis
Fam170a-deleted
mice.
Mechanistically,
found
interacts
remodeling-associated
proteins
regulates
genes
related
remodeling.
Notably,
directly
deubiquitinating
enzyme
Usp7
facilitates
its
translocation
elongating
sperm,
enhancing
activity
on
testis-specific
H2A
H2B
variants.
Collectively,
our
findings
identify
as
previously
unrecognized
regulator
suggest
deubiquitination
may
play
an
essential
Cell Research,
Год журнала:
2021,
Номер
31(6), С. 613 - 630
Опубликована: Янв. 29, 2021
Organization
of
the
genome
into
euchromatin
and
heterochromatin
appears
to
be
evolutionarily
conserved
relatively
stable
during
lineage
differentiation.
In
an
effort
unravel
basic
principle
underlying
folding,
here
we
focus
on
itself
report
a
fundamental
role
for
L1
(LINE1
or
LINE-1)
B1/Alu
retrotransposons,
most
abundant
subclasses
repetitive
sequences,
in
chromatin
compartmentalization.
We
find
that
homotypic
clustering
demarcates
grossly
exclusive
domains,
characterizes
predicts
Hi-C
compartments.
Spatial
segregation
L1-rich
sequences
nuclear
nucleolar
peripheries
B1/Alu-rich
interior
is
mouse
human
cells
occurs
dynamically
cell
cycle.
addition,
de
novo
establishment
B1
coincident
with
formation
higher-order
structures
early
embryogenesis
critically
regulated
by
transcripts.
Importantly,
depletion
transcripts
embryonic
stem
drastically
weakens
repeat
contacts
compartmental
strength,
disrupts
L1-
B1-rich
chromosomal
at
genome-wide
individual
sites.
Mechanistically,
co-localization
liquid
droplet
DNA
RNA
protein
HP1α
suggest
phase-separation
mechanism
which
promotes
Taken
together,
propose
genetically
encoded
model
repeats
blueprint
macrostructure.
Our
explains
robustness
folding
common
core,
dynamic
gene
regulation
overlaid
across
cells.
B-type
lamins
are
critical
nuclear
envelope
proteins
that
interact
with
the
three-dimensional
genomic
architecture.
However,
identifying
direct
roles
of
B-lamins
on
dynamic
genome
organization
has
been
challenging
as
their
joint
depletion
severely
impacts
cell
viability.
To
overcome
this,
we
engineered
mammalian
cells
to
rapidly
and
completely
degrade
endogenous
using
Auxin-inducible
degron
technology.
Journal of Cellular Biochemistry,
Год журнала:
2024,
Номер
125(3)
Опубликована: Фев. 12, 2024
Abstract
Mechanical
forces
may
be
generated
within
a
cell
due
to
tissue
stiffness,
cytoskeletal
reorganization,
and
the
changes
(even
subtle)
in
cell's
physical
surroundings.
These
of
impose
mechanical
tension
intracellular
protein
network
(both
cytosolic
nuclear).
could
released
by
series
protein–protein
interactions
often
facilitated
membrane
lipids,
lectins
sugar
molecules
thus
generate
type
signal
drive
cellular
processes,
including
differentiation,
polarity,
growth,
adhesion,
movement,
survival.
Recent
experimental
data
have
accentuated
molecular
mechanism
this
transduction
pathway,
dubbed
mechanotransduction.
Mechanosensitive
proteins
plasma
discern
channel
information
interior.
Cells
respond
message
altering
their
arrangement
directly
transmitting
nucleus
through
connection
cytoskeleton
nucleoskeleton
before
despatched
biochemical
signaling
pathways.
Nuclear
transmission
force
leads
activation
chromatin
modifiers
modulation
epigenetic
landscape,
inducing
reorganization
gene
expression
regulation;
time
chemical
messengers
(transcription
factors)
arrive
into
nucleus.
While
significant
research
has
been
done
on
role
mechanotransduction
tumor
development
cancer
progression/metastasis,
mechanistic
basis
force‐activated
carcinogenesis
is
still
enigmatic.
Here,
review,
we
discussed
various
cues
connections
better
comprehend
also
explored
detailed
some
multiple
players
(proteins
macromolecular
complexes)
involved
Thus,
described
an
avenue:
how
stress
directs
modulate
epigenome
cells
aberrant
phenotype.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(6), С. 3178 - 3178
Опубликована: Март 20, 2021
In
eukaryotic
cells,
the
nucleus
houses
genomic
material
of
cell.
The
physical
properties
and
its
ability
to
sense
external
mechanical
cues
are
tightly
linked
regulation
cellular
events,
such
as
gene
expression.
Nuclear
mechanics
morphology
altered
in
many
diseases
cancer
premature
ageing
syndromes.
Therefore,
it
is
important
understand
how
different
components
contribute
nuclear
processes,
organisation
mechanics,
they
misregulated
disease.
Although,
over
years,
studies
have
focused
on
lamina—a
mesh
intermediate
filament
proteins
residing
between
chromatin
membrane—there
growing
evidence
that
structure
factors
regulate
essential
contributors
nucleus.
Here,
we
review
main
structural
nucleus,
with
particular
emphasis
structure.
We
also
provide
an
example
stiffness
can
both
impact
be
affected
by
processes
DNA
damage
repair.
