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Acetylation changes at lysine 5 of histone H4 associated with lytic gene promoters during reactivation of Kaposi's sarcoma-associated herpesvirus.
[primary effusion lymphoma]
Kaposi
's
sarcoma
-associated
herpesvirus
(
KSHV
)
is
a
pathogenic
agent
of
Kaposi
's
sarcoma
,
primary
effusion
lymphoma
and
multicentric
Castleman
's
disease
in
humans
.
Similarly
to
other
gammaherpesviruses
such
as
Epstein-
Barr
virus
(
EBV
)
and
herpesvirus
saimiri
(
HVS
)
,
KSHV
displays
two
alternative
life
cycles
,
latent
and
lytic
one
.
The
transactivation
from
latency
to
the
lytic
phase
is
the
result
of
transcriptional
changes
in
the
KSHV
genome
caused
by
the
replication
and
transcriptional
activator
(
RTA
)
.
During
KSHV
reactivation
,
epigenetic
modifications
of
histone
protein
on
the
viral
genome
occur
,
which
regulate
the
transcriptional
activation
of
a
number
of
lytic
genes
.
The
reactivation
of
EBV
from
latency
to
lytic
cycle
,
induced
by
an
immediate-
early
Zta
protein
,
was
shown
to
be
accompanied
by
acetylation
of
specific
lysines
in
histone
H
4
.
Accordingly
,
we
hypothesized
that
the
RTA-induced
transactivation
of
KSHV
could
also
be
accompanied
by
histone
acetylation
.
To
validate
this
hypothesis
,
we
assayed
alterations
of
acetyl-histone
H
4
-
lysine
5
(
acH
4
K
5
)
during
the
RTA-mediated
KSHV
reactivation
.
While
the
modified
histone
protein
in
a
total
cell
lysate
was
not
distinguished
between
control
and
RTA-expressed
cells
,
upregulated
acH
4
K
5
was
detected
on
several
lytic
gene
promoter
regions
during
KSHV
reactivation
.
Our
results
clearly
indicate
that
this
epigenetic
change
is
related
to
transcription
of
genes
expressed
in
the
lytic
cycle
of
KSHV
.
Diseases
Validation
Diseases presenting
"several lytic gene promoter regions"
symptom
primary effusion lymphoma
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