The Journal of Experimental Medicine,
Journal Year:
2024,
Volume and Issue:
222(3)
Published: Dec. 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
Nucleus,
Journal Year:
2022,
Volume and Issue:
13(1), P. 238 - 278
Published: Nov. 20, 2022
Access
to
DNA
is
a
prerequisite
the
execution
of
essential
cellular
processes
that
include
transcription,
replication,
chromosomal
segregation,
and
repair.
How
proteins
regulate
these
function
in
context
chromatin
its
dynamic
architectures
an
intensive
field
study.
Over
past
decade,
genome-wide
assays
new
imaging
approaches
have
enabled
greater
understanding
how
access
genome
regulated
by
nucleosomes
associated
proteins.
Additional
mechanisms
may
control
accessibility
vivo
compaction
phase
separation
–
are
beginning
be
understood.
Here,
we
review
ongoing
development
measurements,
summarize
different
molecular
structural
shape
landscape,
detail
many
important
biological
functions
linked
accessibility.
Cell stem cell,
Journal Year:
2023,
Volume and Issue:
30(12), P. 1569 - 1584
Published: Oct. 18, 2023
Studies
of
mammalian
development
have
advanced
our
understanding
the
genetic,
epigenetic,
and
cellular
processes
that
orchestrate
embryogenesis
uncovered
new
insights
into
unique
aspects
human
embryogenesis.
Recent
studies
now
produced
first
epigenetic
maps
early
embryogenesis,
stimulating
ideas
about
reprogramming,
cell
fate
control,
potential
mechanisms
underpinning
developmental
plasticity
in
embryos.
In
this
review,
we
discuss
these
regulation
importance
for
safeguarding
development.
We
also
highlight
unanswered
questions
key
challenges
remain
to
be
addressed.
Nature Reviews Genetics,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 12, 2024
The
DNA
methylation
field
has
matured
from
a
phase
of
discovery
and
genomic
characterization
to
one
seeking
deeper
functional
understanding
how
this
modification
contributes
development,
ageing
disease.
In
particular,
the
past
decade
seen
many
exciting
mechanistic
discoveries
that
have
substantially
expanded
our
appreciation
for
generic,
evolutionarily
ancient
can
be
incorporated
into
robust
epigenetic
codes.
Here,
we
summarize
current
distinct
landscapes
emerge
over
mammalian
lifespan
discuss
they
interact
with
other
regulatory
layers
support
diverse
functions.
We
then
review
rising
interest
in
alternative
patterns
found
during
senescence
somatic
transition
cancer.
Alongside
advancements
single-cell
long-read
sequencing
technologies,
collective
insights
made
across
these
fields
offer
new
opportunities
connect
biochemical
genetic
features
cell
physiology,
developmental
potential
phenotype.
Review,
Smith
et
al.
describe
development
within
key
disease
states,
as
well
different
methyltransferases
interface
histone
modifications
proteins
create
maintain
them.
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(18)
Published: May 3, 2024
In
mammals,
males
and
females
show
marked
differences
in
immune
responses.
Males
are
globally
more
sensitive
to
infectious
diseases,
while
susceptible
systemic
autoimmunity.
X-chromosome
inactivation
(XCI),
the
epigenetic
mechanism
ensuring
silencing
of
one
X
females,
may
participate
these
sex
biases.
We
perturbed
expression
trigger
XCI,
noncoding
RNA
Xist
,
female
mice.
This
resulted
reactivation
genes
on
inactive
X,
including
members
Toll-like
receptor
7
(TLR7)
signaling
pathway,
monocyte/macrophages
dendritic
B
cells.
Consequently,
mice
spontaneously
developed
inflammatory
signs
typical
lupus,
anti–nucleic
acid
autoantibodies,
increased
frequencies
age-associated
germinal
center
cells,
expansion
Mechanistically,
TLR7
is
dysregulated
macrophages,
leading
sustained
target
upon
stimulation.
These
findings
provide
a
direct
link
between
maintenance
XCI
female-biased
autoimmune
manifestations
highlight
altered
as
cause
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(10)
Published: March 5, 2025
Women
live
longer
than
men
and
exhibit
less
cognitive
aging.
The
X
chromosome
contributes
to
sex
differences,
as
females
harbor
an
inactive
(Xi)
active
(Xa),
in
contrast
males
with
only
Xa.
Thus,
reactivation
of
silent
Xi
genes
may
contribute
differences.
We
use
allele-specific,
single-nucleus
RNA
sequencing
show
that
aging
remodels
transcription
the
Xa
across
hippocampal
cell
types.
Aging
preferentially
changed
gene
expression
on
X's
relative
autosomes.
Select
underwent
activation,
new
escape
cells
including
dentate
gyrus,
critical
learning
memory.
Expression
escapee
Plp1,
a
myelin
component,
was
increased
hippocampus
female
mice
parahippocampus
women.
AAV-mediated
Plp1
elevation
gyrus
male
improved
cognition.
Understanding
how
confer
advantage
could
lead
novel
targets
counter
brain
disease
both
sexes.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Feb. 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.
Trends in Genetics,
Journal Year:
2022,
Volume and Issue:
39(2), P. 125 - 139
Published: Sept. 19, 2022
Mitochondria,
organelles
that
harbor
their
own
circular
genomes,
are
critical
for
energy
production
and
homeostasis
maintenance
in
eukaryotic
cells.
Recent
studies
discovered
hundreds
of
mitochondria-encoded
noncoding
RNAs
(mt-ncRNAs),
including
novel
subtypes
(mecciRNAs)
double-stranded
(mt-dsRNAs).
Here,
we
discuss
the
emerging
field
mt-ncRNAs
by
reviewing
expression
patterns,
biogenesis,
metabolism,
regulatory
roles,
functional
mechanisms.
Many
have
roles
cellular
physiology,
some
associated
with,
or
even
act
as,
causal
factors
human
diseases.
We
also
highlight
developments
technologies
methodologies
further
insights
into
future
perspectives
challenges
studying
these
RNAs,
as
well
potential
biomedical
applications.
