The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
222(3)
Опубликована: Дек. 13, 2024
Systemic
sclerosis
(SSc)
is
an
autoimmune
disease
that
has
a
strong
female
predominance.
Both
the
X-linked
TLR7
and
TLR8
can
induce
type
I
IFN
(IFN-I)
by
plasmacytoid
DCs
(pDCs),
which
promote
fibrosis.
We
identified
five
subclusters
of
pDCs,
including
ISGhigh
clusters
were
over-represented
in
SSc
patients.
observed
both
genes
escape
from
X
chromosome
inactivation
(XCI)
at
higher
frequency
pDCs
patients,
was
associated
with
changes
protein
profile.
Combined
DNA/RNA
FISH
analysis
revealed
TLR7/8
locus
preferentially
located
outside
inactive
(Xi)
territory
when
expressed,
suggesting
higher-order
loop
formation
linked
to
expression
Xi.
Furthermore,
levels
XIST
transcriptional
repressor
SPEN
reduced
pDCs.
Hence,
our
data
heterogeneity
suggested
altered
XCI
may
contribute
chronic
IFN-I
activity
Chemical Reviews,
Год журнала:
2024,
Номер
124(8), С. 4734 - 4777
Опубликована: Апрель 5, 2024
This
comprehensive
Review
delves
into
the
chemical
principles
governing
RNA-mediated
crowding
events,
commonly
referred
to
as
granules
or
biological
condensates.
We
explore
pivotal
role
played
by
RNA
sequence,
structure,
and
modifications
in
these
processes,
uncovering
their
correlation
with
phenomena
under
physiological
conditions.
Additionally,
we
investigate
instances
where
deviates
from
its
intended
function,
leading
pathological
consequences.
By
deepening
our
understanding
of
delicate
balance
that
governs
molecular
driven
implications
for
cellular
homeostasis,
aim
shed
light
on
this
intriguing
area
research.
Our
exploration
extends
methodologies
employed
decipher
composition
structural
intricacies
granules,
offering
a
overview
techniques
used
characterize
them,
including
relevant
computational
approaches.
Through
two
detailed
examples
highlighting
significance
noncoding
RNAs,
NEAT1
XIST,
formation
phase-separated
assemblies
influence
landscape,
emphasize
crucial
organization
function.
elucidating
underpinnings
crowding,
investigating
modifications,
structures,
exploring
both
aberrant
phase
separation
phenomena,
provides
multifaceted
world
Science,
Год журнала:
2024,
Номер
384(6691), С. 53 - 59
Опубликована: Апрель 4, 2024
Genomic
DNA
that
resides
in
the
nuclei
of
mammalian
neurons
can
be
as
old
organism
itself.
The
life
span
nuclear
RNAs,
which
are
critical
for
proper
chromatin
architecture
and
transcription
regulation,
has
not
been
determined
adult
tissues.
In
this
work,
we
identified
characterized
RNAs
do
turn
over
at
least
2
years
a
subset
postnatally
born
cells
mouse
brain.
These
long-lived
were
stably
retained
neural
cell
type–specific
manner
required
maintenance
heterochromatin.
Thus,
may
depend
on
both
molecular
longevity
storage
genetic
information
also
extreme
stability
RNA
functional
organization
chromatin.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 18, 2025
DNA
methylation
at
cytosine
bases
(5-methylcytosine,
5mC)
is
a
heritable
epigenetic
mark
regulating
gene
expression.
While
enzymes
that
metabolize
5mC
are
well-characterized,
endogenous
signaling
molecules
regulate
machinery
have
not
been
described.
We
report
physiological
nitric
oxide
(NO)
concentrations
reversibly
inhibit
the
demethylases
TET
and
ALKBH2
by
binding
to
mononuclear
non-heme
iron
atom
forming
dinitrosyliron
complex
(DNIC)
preventing
cosubstrates
from
binding.
In
cancer
cells
treated
with
exogenous
NO,
or
endogenously
synthesizing
5-hydroxymethylcytosine
(5hmC)
increase,
no
changes
in
methyltransferase
activity.
also
significantly
increased
NO-producing
patient-derived
xenograft
tumors
mice.
Genome-wide
methylome
analysis
of
chronically
NO
(10
days)
shows
enrichment
5hmC
gene-regulatory
loci,
correlating
altered
expression
NO-regulated
tumor-associated
genes.
Regulation
distinctly
different
canonical
represents
unique
role
for
NO.
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(4)
Опубликована: Март 6, 2025
Sex
differences
in
immunity
are
well-documented,
though
mechanisms
underpinning
these
remain
ill-defined.
Here,
a
human-only
ex
vivo
study,
we
demonstrate
that
postpubertal
cisgender
females
have
higher
levels
of
CD19+CD27+IgD−
class-switched
memory
B
cells
compared
with
age-matched
males.
This
increase
is
only
observed
after
puberty
and
before
menopause,
suggesting
strong
influence
for
sex
hormones.
Accordingly,
express
high
estrogen
receptor
2
(ESR2),
class-switch–regulating
genes
enriched
ESR2-binding
sites.
In
gender-diverse
cohort,
blockade
natal
transgender
males
(XX
karyotype)
reduced
cell
frequency,
while
gender-affirming
estradiol
treatment
(XY
did
not
levels.
postmenopausal
cis-females,
were
increased
those
taking
hormone
replacement
therapy
(HRT)
who
not.
These
data
hormones
chromosomes
work
tandem
to
impact
immune
responses,
influencing
the
frequency
individuals
an
XX
chromosomal
background.
Nucleic Acids Research,
Год журнала:
2023,
Номер
51(5), С. 2177 - 2194
Опубликована: Фев. 2, 2023
Abstract
X
chromosome
inactivation
(XCI)
is
an
essential
process,
yet
it
initiates
with
remarkable
diversity
in
various
mammalian
species.
XIST,
the
main
trigger
of
XCI,
controlled
mouse
by
interplay
lncRNA
genes
(LRGs),
some
which
evolved
concomitantly
to
XIST
and
have
orthologues
across
all
placental
mammals.
Here,
we
addressed
functional
conservation
human
two
such
LRGs,
FTX
JPX.
By
combining
analysis
single-cell
RNA-seq
data
from
early
embryogenesis
assays
matched
pluripotent
stem-
or
differentiated
post-XCI
cells,
demonstrate
major
differences
for
these
between
species,
independently
primary
sequence
conservation.
While
function
not
conserved
humans,
JPX
stands
as
a
regulator
expression
both
However,
show
that
different
entities
control
production
at
steps
depending
on
Altogether,
our
study
highlights
versatility
LRGs
evolution,
reveals
orthologous
may
involve
diversified
mechanisms
action.
These
findings
represent
striking
example
how
evolvability
can
provide
adaptative
flexibility
constrained
gene
regulatory
networks.
Chromosome Research,
Год журнала:
2023,
Номер
31(3)
Опубликована: Авг. 25, 2023
Mistakes
in
chromosome
segregation
leading
to
aneuploidy
are
the
primary
cause
of
miscarriages
humans.
Excluding
sex
chromosomes,
viable
aneuploidies
humans
include
trisomies
chromosomes
21,
18,
or
13,
which
Down,
Edwards,
Patau
syndromes,
respectively.
While
individuals
with
trisomy
18
13
die
soon
after
birth,
people
Down
syndrome
live
adulthood
but
have
intellectual
disabilities
and
prone
multiple
diseases.
At
cellular
level,
mistakes
a
single
cell
losing
lethal.
In
contrast,
that
gains
can
survive.
Several
studies
support
hypothesis
gaining
an
extra
copy
causes
gene-specific
phenotypes
independent
identity
genes
encoded
within
chromosome.
The
latter,
referred
as
aneuploidy-associated
phenotypes,
focus
this
review.
Among
conserved
observed
yeast
human
cells
lower
viability,
increased
gene
expression,
protein
synthesis
turnover,
abnormal
nuclear
morphology,
altered
metabolism.
Notably,
morphology
aneuploid
is
associated
metabolic
demand
for
de
novo
sphingolipids.
These
findings
reveal
important
insights
into
possible
pathological
role
syndrome.
Despite
adverse
effects
on
physiology,
hallmark
cancer
cells.
Understanding
how
affects
physiology
selective
pressure
must
overcome
unlimited
proliferation.
