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
Cell
memory
refers
to
the
capacity
of
cells
maintain
their
gene
expression
program
once
initiating
environmental
signal
has
ceased.
This
exceptional
feature
is
key
during
formation
mammalian
organisms,
and
it
believed
be
in
part
mediated
by
epigenetic
factors
that
can
endorse
with
landmarks
required
transcriptional
programs
upon
cell
duplication.
Here,
we
review
current
literature
analyzing
molecular
basis
mammals,
a
focus
on
mechanisms
which
transcriptionally
repressive
chromatin
modifications
such
as
methylation
DNA
histone
H3
are
propagated
through
mitotic
divisions.
The
emerging
picture
suggests
cellular
supported
an
cycle
reversible
activities
carried
out
regulators
coordination
transition
create
multiphasic
system
accommodate
both
maintenance
identity
differentiation
proliferating
stem
populations.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 16, 2024
Abstract
Most
human
cells
contain
two
non-identical
genomes,
and
differences
in
their
regulation
underlie
development
disease.
We
demonstrate
that
Fiber-seq
Inferred
Regulatory
Elements
(FIREs)
enable
the
accurate
quantification
of
chromatin
accessibility
across
6
Gbp
diploid
genome
with
single-molecule
single-nucleotide
precision.
find
can
harbor
>1,000
regulatory
elements
haplotype-selective
(HSCA)
show
these
preferentially
localize
to
genomic
loci
containing
most
genetic
diversity,
leukocyte
antigen
(HLA)
locus
showing
largest
amount
HSCA
genome-wide
immune
cells.
Furthermore,
we
uncover
sequence
non-deterministic
accessibility,
representing
likely
somatic
epimutations,
productive
transcription
from
inactive
X
chromosome
is
buttressed
by
clustered
promoter-proximal
escape
inactivation.
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
