The EMBO Journal,
Journal Year:
2022,
Volume and Issue:
41(22)
Published: Oct. 10, 2022
Abstract
Epigenome
reprogramming
after
fertilization
enables
transcriptionally
quiescent
maternal
and
paternal
chromatin
to
acquire
a
permissive
state
for
subsequent
zygotic
genome
activation
(ZGA).
H3K27
acetylation
(H3K27ac)
is
well‐established
marker
of
active
enhancers
promoters.
However,
dynamics
H3K27ac
during
maternal‐to‐zygotic
transition
(MZT)
in
mammalian
embryos
are
not
well‐studied.
By
profiling
the
allelic
landscape
mouse
MZT,
we
show
that
undergoes
three
waves
rapid
global
transitions
between
oocyte
stage
2‐cell
stage.
Notably,
germinal
vesicle
zygote
globally
hyperacetylated,
with
noncanonical,
broad
domains
correlate
H3K4
trimethylation
(H3K4me3)
open
chromatin.
marks
genomic
regions
primed
including
ZGA
genes,
retrotransposons,
alleles
imprinted
genes.
We
CBP/p300
HDAC
activities
play
important
roles
regulating
essential
preimplantation
development.
Specifically,
acetyltransferase
broadly
deposits
zygotes
induce
opening
condensed
at
putative
ensure
proper
ZGA.
On
contrary,
HDACs
revert
canonical
safeguard
by
preventing
premature
expression
developmental
In
conclusion,
coordinated
MZT
Nature Genetics,
Journal Year:
2024,
Volume and Issue:
56(6), P. 1168 - 1180
Published: May 9, 2024
Abstract
Chromatin
modifications
are
linked
with
regulating
patterns
of
gene
expression,
but
their
causal
role
and
context-dependent
impact
on
transcription
remains
unresolved.
Here
we
develop
a
modular
epigenome
editing
platform
that
programs
nine
key
chromatin
modifications,
or
combinations
thereof,
to
precise
loci
in
living
cells.
We
couple
this
single-cell
readouts
systematically
quantitate
the
magnitude
heterogeneity
transcriptional
responses
elicited
by
each
specific
modification.
Among
these,
show
installing
histone
H3
lysine
4
trimethylation
(H3K4me3)
at
promoters
can
causally
instruct
hierarchically
remodeling
landscape.
further
dissect
how
DNA
sequence
motifs
influence
marks,
identifying
switch-like
attenuative
effects
within
distinct
cis
contexts.
Finally,
examine
interplay
combinatorial
revealing
co-targeted
H3K27
(H3K27me3)
H2AK119
monoubiquitination
(H2AK119ub)
maximizes
silencing
penetrance
across
single
Our
precision-perturbation
strategy
unveils
principles
modification(s)
dissects
quantitative
calibrated
contextual
interactions.
Antioxidants and Redox Signaling,
Journal Year:
2023,
Volume and Issue:
39(7-9), P. 491 - 511
Published: May 11, 2023
Aims:
Lipid
peroxidation
occurring
in
lung
adenocarcinoma
(LUAD)
cells
leads
to
ferroptosis.
Lysophosphatidylcholine
acyl-transferase
3
(LPCAT3)
plays
a
key
role
providing
raw
materials
for
lipid
by
promoting
esterification
of
polyunsaturated
fatty
acids
phospholipids.
Whether
LPCAT3
determines
ferroptosis
sensitivity
and
the
mechanism
which
its
expression
is
regulated
LUAD
has
not
been
reported.
Results:
acyl-coenzyme
A
(CoA)
synthetase
long-chain
family
member
(ACSL)4
levels
were
positively
associated
with
cell
lines.
Overexpression
ACSL4
sensitized
ferroptosis,
while
knockout
showed
opposite
effect.
Zinc-finger
E-box-binding
(ZEB)
was
shown
directly
bind
promoter
stimulate
transcription
Yes-associated
protein
(YAP)-dependent
manner.
An
interaction
between
YAP
ZEB
also
observed.
E1A-binding
p300
(EP300)
simultaneously
bound
ZEB,
induced
H3K27Ac
transcription.
This
verified
primary
xenograft
models.
The
ACSL4,
LPCAT3,
combination
can
jointly
determine
sensitivity.
Innovation:
binding
site
exists
-1600
-1401
nt
region
promoter,
promotes
after
binding.
bind,
zinc-finger
cluster
domain
WW
are
crucial
their
EP300
may
via
Bromo
CBP/p300-HAT
domain.
In
addition,
better
than
prostaglandin-endoperoxide
synthase
2
(PTGS2),
transferrin
receptor
(TFRC),
or
NADPH
oxidase
1
(NOX1).
Conclusion:
YAP,
EP300.
be
determined
YAP.
Antioxid.
Redox
Signal.
39,
491-511.
Nature,
Journal Year:
2024,
Volume and Issue:
627(8004), P. 671 - 679
Published: March 6, 2024
Abstract
DNA
and
histone
modifications
combine
into
characteristic
patterns
that
demarcate
functional
regions
of
the
genome
1,2
.
While
many
‘readers’
individual
have
been
described
3–5
,
how
chromatin
states
comprising
composite
modification
signatures,
variants
internucleosomal
linker
are
interpreted
is
a
major
open
question.
Here
we
use
multidimensional
proteomics
strategy
to
systematically
examine
interaction
around
2,000
nuclear
proteins
with
over
80
modified
dinucleosomes
representing
promoter,
enhancer
heterochromatin
states.
By
deconvoluting
complex
nucleosome-binding
profiles
networks
co-regulated
distinct
nucleosomal
features
driving
protein
recruitment
or
exclusion,
show
comprehensively
decoded
by
readers.
We
find
highly
distinctive
binding
responses
different
features,
factors
recognize
multiple
operate
largely
independently
in
regulating
chromatin.
Our
online
resource,
Modification
Atlas
Regulation
Chromatin
States
(MARCS),
provides
in-depth
analysis
tools
engage
our
results
advance
discovery
fundamental
principles
regulation
Nature Genetics,
Journal Year:
2023,
Volume and Issue:
55(4), P. 679 - 692
Published: April 1, 2023
Abstract
Chromatin
features
are
widely
used
for
genome-scale
mapping
of
enhancers.
However,
discriminating
active
enhancers
from
other
cis
-regulatory
elements,
predicting
enhancer
strength
and
identifying
their
target
genes
is
challenging.
Here
we
establish
histone
H2B
N-terminus
multisite
lysine
acetylation
(H2BNTac)
as
a
signature
H2BNTac
prominently
marks
candidate
subset
promoters
discriminates
them
ubiquitously
promoters.
Two
mechanisms
underlie
the
distinct
specificity:
(1)
unlike
H3K27ac,
specifically
catalyzed
by
CBP/p300;
(2)
H2A–H2B,
but
not
H3–H4,
rapidly
exchanged
through
transcription-induced
nucleosome
remodeling.
H2BNTac-positive
show
high
validation
rate
in
orthogonal
activity
assays
vast
majority
endogenously
marked
H3K27ac.
Notably,
intensity
predicts
outperforms
current
state-of-the-art
models
CBP/p300
genes.
These
findings
have
broad
implications
generating
fine-grained
maps
modeling
CBP/p300-dependent
gene
regulation.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(16)
Published: April 21, 2023
Zygotic
genome
activation
(ZGA)
is
a
crucial
step
of
embryonic
development.
So
far,
little
known
about
the
role
chromatin
factors
during
this
process.
Here,
we
used
an
in
vivo
RNA
interference
reverse
genetic
screen
to
identify
necessary
for
development
Drosophila
melanogaster
.
Our
reveals
that
histone
acetyltransferases
(HATs)
and
deacetylases
are
ZGA
regulators.
We
demonstrate
Nejire
(CBP/EP300
ortholog)
essential
acetylation
H3
lysine-18
lysine-27,
whereas
Gcn5
(GCN5/PCAF
lysine-9
at
ZGA,
with
these
marks
being
enriched
all
actively
transcribed
genes.
Nonetheless,
HATs
activate
distinct
sets
Unexpectedly,
individual
catalytic
dead
mutants
either
or
can
zygotic
transcription
transactivate
reporter
gene
vitro.
Together,
our
data
as
key
regulators
ZGA.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(16)
Published: April 21, 2023
The
past
three
decades
have
yielded
a
wealth
of
information
regarding
the
chromatin
regulatory
mechanisms
that
control
transcription.
“histone
code”
hypothesis—which
posits
distinct
combinations
posttranslational
histone
modifications
are
“read”
by
downstream
effector
proteins
to
regulate
gene
expression—has
guided
research
uncover
fundamental
relevant
many
aspects
biology.
However,
recent
molecular
and
genetic
studies
revealed
function
histone-modifying
enzymes
extends
independently
beyond
their
catalytic
activities.
In
this
review,
we
highlight
original
advances
in
understanding
noncatalytic
functions
modifiers.
Many
deposited
these
enzymes—previously
considered
be
required
for
transcriptional
activation—have
been
demonstrated
dispensable
expression
living
organisms.
This
perspective
aims
prompt
further
examination
enigmatic
inspiring
define
“epigenetic
moonlighting”
chromatin-modifying
enzymes.
Nucleus,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Jan. 5, 2023
Enhancers
are
cis-regulatory
elements
that
can
stimulate
gene
expression
from
distance,
and
drive
precise
spatiotemporal
profiles
during
development.
Functional
enhancers
display
specific
features
including
an
open
chromatin
conformation,
Histone
H3
lysine
27
acetylation,
4
mono-methylation
enrichment,
enhancer
RNAs
production.
These
modified
upon
developmental
cues
which
impacts
their
activity.
In
this
review,
we
describe
the
current
state
of
knowledge
about
functions
diverse
signatures
found
on
enhancers.
We
also
discuss
dynamic
changes
signatures,
impact
lineage
profiles,
development
or
cellular
differentiation.
