Nucleic Acids Research,
Год журнала:
2022,
Номер
51(2), С. e8 - e8
Опубликована: Ноя. 9, 2022
A
major
challenge
in
single-cell
biology
is
identifying
cell-type-specific
gene
functions,
which
may
substantially
improve
precision
medicine.
Differential
expression
analysis
of
genes
a
popular,
yet
insufficient
approach,
and
complementary
methods
that
associate
function
with
cell
type
are
required.
Here,
we
describe
scHumanNet
(https://github.com/netbiolab/scHumanNet),
network
platform
for
resolving
cellular
heterogeneity
across
functions
humans.
Based
on
networks
(CGNs)
constructed
under
the
guidance
HumanNet
reference
interactome,
displayed
higher
functional
relevance
to
context
than
CGNs
built
by
other
transcriptome
data.
Cellular
deconvolution
signatures
based
compactness
types
revealed
breast
cancer
prognostic
markers
associated
T
cells.
could
also
prioritize
particular
using
CGN
centrality
identified
differential
hubness
between
disease
healthy
conditions.
We
demonstrated
usefulness
uncovering
T-cell-specific
effects
GITR,
cancer,
defects
autism
spectrum
disorder
specific
inhibitory
neurons.
These
results
suggest
will
advance
our
understanding
cell-type
specificity
human
genes.
Cells,
Год журнала:
2022,
Номер
11(4), С. 748 - 748
Опубликована: Фев. 21, 2022
Methyl-CpG-binding
protein
2
(MeCP2)
is
a
transcriptional
regulator
that
highly
abundant
in
the
brain.
It
binds
to
methylated
genomic
DNA
regulate
range
of
physiological
functions
implicated
neuronal
development
and
adult
synaptic
plasticity.
MeCP2
has
mainly
been
studied
for
its
role
neurodevelopmental
disorders,
but
alterations
are
also
present
stress-related
disorders
such
as
major
depression.
Impairments
both
stress
regulation
plasticity
associated
with
depression,
specific
mechanisms
underlying
these
changes
have
not
identified.
Here,
we
review
interplay
between
stress,
plasticity,
MeCP2.
We
focus
our
attention
on
important
genes
BDNF
reelin
(RELN).
Moreover,
provide
evidence
from
recent
studies
showing
link
chronic
stress-induced
depressive
symptoms
dysregulation
expression,
underscoring
this
pathology.
conclude
promising
target
novel,
more
efficacious
therapeutics
treatment
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Авг. 22, 2023
Oncogene-induced
DNA
replication
stress
(RS)
and
consequent
pathogenic
R-loop
formation
are
known
to
impede
S
phase
progression.
Nonetheless,
cancer
cells
continuously
proliferate
under
such
high-stressed
conditions
through
incompletely
understood
mechanisms.
Here,
we
report
taurine
upregulated
gene
1
(TUG1)
long
noncoding
RNA
(lncRNA),
which
is
highly
expressed
in
many
types
of
cancers,
as
an
important
regulator
intrinsic
cells.
Under
RS
conditions,
TUG1
rapidly
via
activation
the
ATR-CHK1
signaling
pathway,
interacts
with
RPA
DHX9,
engages
resolving
R-loops
at
certain
loci,
particularly
CA
repeat
microsatellite
loci.
Depletion
leads
overabundant
enhanced
RS,
leading
substantial
inhibition
tumor
growth.
Our
data
reveal
a
role
molecule
for
accumulation
suggest
targeting
potent
therapeutic
approach
treatment.
Mutations
in
the
X-linked
methyl-CpG-binding
protein
2
(MECP2)
gene
cause
Rett
syndrome,
a
severe
childhood
neurological
disorder.
MeCP2
is
well-established
transcriptional
repressor,
yet
upon
its
loss,
hundreds
of
genes
are
dysregulated
both
directions.
To
understand
what
drives
such
dysregulation,
we
deleted
Mecp2
adult
mice,
circumventing
developmental
contributions
and
secondary
pathogenesis.
We
performed
time
series
transcriptional,
chromatin,
phenotypic
analyses
hippocampus
to
determine
immediate
consequences
loss
cascade
find
that
causes
bidirectional
progressive
dysregulation
transcriptome.
downregulation,
profiled
genome-wide
histone
modifications
found
decrease
H3
acetylation
(ac)
at
downregulated
among
earliest
molecular
changes
occurring
well
before
any
measurable
deficiencies
electrophysiology
function.
These
data
reveal
disease
independent
or
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Окт. 1, 2021
Abstract
Rett
syndrome
(RTT)
is
a
severe
neurological
disorder
and
leading
cause
of
intellectual
disability
in
young
females.
RTT
mainly
caused
by
mutations
found
the
X-linked
gene
encoding
methyl-CpG
binding
protein
2
(MeCP2).
Despite
extensive
studies,
molecular
mechanism
underlying
pathogenesis
still
poorly
understood.
Here,
we
report
MeCP2
as
key
subunit
higher-order
multiunit
complex
Rbfox/LASR.
Defective
mouse
models
disrupts
assembly
MeCP2/Rbfox/LASR
complex,
to
reduced
Rbfox
proteins
target
pre-mRNAs
aberrant
splicing
Nrxns
Nlgn1
critical
for
synaptic
plasticity.
We
further
show
that
disease
mutants
display
defective
condensate
properties
fail
promote
phase-separated
condensates
with
vitro
cultured
cells.
These
data
link
an
impaired
function
mutation
control
its
mediating
complex.
Biology of the Cell,
Год журнала:
2022,
Номер
115(1)
Опубликована: Сен. 19, 2022
As
the
repository
of
genetic
information,
cell
nucleus
must
protect
DNA
integrity
from
mechanical
stresses.
The
nuclear
lamina,
which
resides
within
envelope
(NE),
is
made
up
lamins,
intermediate
filaments
bound
to
DNA.
lamina
provides
with
ability
deal
inward
as
well
outward
stimuli.
Chromatin,
in
turn,
through
its
degrees
compaction,
shares
this
role
thus,
ensuring
plasticity
nucleus.
Perturbation
chromatin
condensation
or
has
been
linked
a
plethora
biological
conditions,
that
range
cancer
and
diseases
(laminopathies)
aging,
both
natural
accelerated,
such
case
Hutchinson‐Gilford
Progeria
Syndrome
(HGPS).
From
experimental
results
accumulated
so
far
on
topic,
direct
link
between
variations
epigenetic
pattern
structure
would
be
suggested,
however,
it
never
clarified
thoroughly.
This
relationship,
instead,
downstream
important
implication
shape,
genome
preservation,
force
sensing,
and,
ultimately,
aging‐related
disease
onset.
With
review,
we
aim
collect
recent
studies
importance
components
status
mechanics.
We
also
bring
light
evidence
methylation
accelerated
aging.
Nature,
Год журнала:
2023,
Номер
624(7991), С. 433 - 441
Опубликована: Ноя. 29, 2023
FOXP3
is
a
transcription
factor
that
essential
for
the
development
of
regulatory
T
cells,
branch
cells
suppress
excessive
inflammation
and
autoimmunity
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 5, 2023
Transcriptional
changes
in
Rett
syndrome
(RTT)
are
assumed
to
directly
correlate
with
steady-state
mRNA
levels,
but
limited
evidence
mice
suggests
that
transcription
can
be
compensated
by
post-transcriptional
regulation.
We
measure
rate
and
half-life
RTT
patient
neurons
using
RATEseq,
re-interpret
nuclear
whole-cell
RNAseq
from
Mecp2
mice.
Genes
dysregulated
changing
or
buffered
when
both
change.
utilized
classifier
models
predict
the
direction
of
find
combined
frequencies
three
dinucleotides
better
predictors
than
CA
CG.
MicroRNA
RNA-binding
Protein
(RBP)
motifs
enriched
3'UTRs
genes
changes.
Nuclear
RBP
on
increased
rate.
identify
mechanisms
humans
alter
buffer
a
transcriptional
modulator
gene
is
mutated
neurodevelopmental
disorder.
