Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(4)
Опубликована: Фев. 14, 2022
The
chromosomal
t(4;14)
(p16;q32)
translocation
drives
high
expression
of
histone
methyltransferase
nuclear
SET
domain-containing
2
(NSD2)
and
plays
vital
roles
in
multiple
myeloma
(MM)
evolution
progression.
However,
the
mechanisms
NSD2-driven
epigenomic
alterations
chemoresistance
to
proteasome
inhibitors
(PIs)
are
not
fully
understood.
Using
a
CRISPR/Cas9
sgRNA
library
bone
marrow-bearing
MM
model,
we
found
that
hepatoma-derived
growth
factor
(HRP2)
was
suppressor
PIs
its
downregulation
correlated
with
poor
response
worse
outcomes
clinic.
We
observed
suppression
HRP2
bortezomib-resistant
cells,
knockdown
induced
marked
tolerance
PIs.
Moreover,
augmented
H3K27me3
levels,
consequentially
intensifying
transcriptome
promoting
cell
survival
restriction
ER
stress.
Mechanistically,
recognized
H3K36me2
recruited
demethylase
MYC-induced
antigen
(MINA)
remove
H3K27me3.
Tazemetostat,
highly
selective
epigenetic
inhibitor
reduces
synergistically
sensitized
anti-MM
effects
bortezomib
both
vitro
vivo.
Collectively,
these
results
provide
better
understanding
origin
patients
rationale
for
managing
who
have
different
genomic
backgrounds.
ABSTRACT
Histone
post-translational
modifications
are
key
gene
expression
regulators,
but
their
rapid
dynamics
during
development
remain
difficult
to
capture.
We
applied
a
Fab-based
live
endogenous
modification
labeling
technique
monitor
the
changes
in
histone
levels
zygotic
genome
activation
(ZGA)
living
zebrafish
embryos.
Among
various
modifications,
H3
Lys27
acetylation
(H3K27ac)
exhibited
most
drastic
changes,
accumulating
two
nuclear
foci
64-
1k-cell-stage
The
elongating
form
of
RNA
polymerase
II,
which
is
phosphorylated
at
Ser2
heptad
repeats
within
C-terminal
domain
(RNAP2
Ser2ph),
and
miR-430
transcripts
were
also
concentrated
closely
associated
with
H3K27ac.
When
treated
α-amanitin
inhibit
transcription
or
JQ-1
binding
acetyl-reader
proteins,
H3K27ac
still
appeared
RNAP2
Ser2ph
morpholino
not
foci,
suggesting
that
precedes
active
ZGA.
anticipate
method
presented
here
could
be
variety
developmental
processes
any
model
non-model
organisms.
Histone
marks
control
many
cellular
processes
including
DNA
damage
repair.
This
review
will
focus
primarily
on
the
active
histone
mark
H3K36me3
in
regulation
of
repair
and
maintenance
genomic
stability
after
damage.
There
are
diverse
clues
showing
participates
response
by
directly
recruiting
machinery
to
set
chromatin
at
a
"ready"
status,
leading
quick
upon
Reduced
is
associated
with
low
efficiency.
also
place
main
emphasis
H3K36me3-mediated
tumorigenesis
newly
found
oncohistone
mutant
tumors.
Gaining
an
understanding
different
aspects
repair,
especially
cancers,
would
share
knowledge
serve
drug
discovery
patient
care.
ASN NEURO,
Год журнала:
2021,
Номер
13, С. 175909142098120 - 175909142098120
Опубликована: Янв. 1, 2021
Expression
of
the
GFAP
gene
has
attracted
considerable
attention
because
its
onset
is
a
marker
for
astrocyte
development,
upregulation
reactive
gliosis,
and
predominance
in
astrocytes
provides
tool
their
genetic
manipulation.
The
literature
on
regulation
voluminous,
as
almost
any
perturbation
development
or
homeostasis
CNS
will
lead
to
changes
expression.
In
this
review,
we
limit
our
discussion
mechanisms
proposed
regulate
synthesis
through
direct
interaction
with
mRNA.
Strengths
weaknesses
supportive
experimental
findings
are
described,
suggestions
made
additional
studies.
This
review
covers
15
transcription
factors,
DNA
histone
methylation,
microRNAs.
complexity
involved
regulating
expression
intermediate
filament
protein
suggests
that
function
may
vary
among
both
subtypes
other
GFAP-expressing
cells,
well
during
response
perturbations.
Current Medicinal Chemistry,
Год журнала:
2021,
Номер
29(14), С. 2399 - 2411
Опубликована: Ноя. 9, 2021
Epigenetic
regulations
play
a
crucial
role
in
the
expression
of
various
genes
that
are
important
normal
cell
function.
Any
alteration
these
epigenetic
mechanisms
can
lead
to
modification
histone
and
DNA,
resulting
silencing
or
enhanced
some
causing
diseases.
Acetylation,
methylation,
ribosylation,
phosphorylation
proteins
modifies
its
interaction
with
consequently
changing
ratio
heterochromatin
euchromatin.
Terminal
lysine
residues
serve
as
potential
targets
such
modifications.
The
current
review
focuses
on
modifications,
their
contributing
factors;
modifications
metabolism
leads
cancer,
methylation
cancer
affects
DNA
repair
mechanisms.
