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The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells.
[wolf-hirschhorn syndrome]
The
multiple
myeloma
SET
domain
(
MMSET
)
protein
is
overexpressed
in
multiple
myeloma
(
MM
)
patients
with
the
translocation
t
(
4
;
14
)
.
Although
studies
have
shown
the
involvement
of
MMSET
/
Wolf-
Hirschhorn
syndrome
candidate
1
in
development
,
its
mode
of
action
in
the
pathogenesis
of
MM
is
largely
unknown
.
We
found
that
MMSET
is
a
major
regulator
of
chromatin
structure
and
transcription
in
t
(
4
;
14
)
MM
cells
.
High
levels
of
MMSET
correlate
with
an
increase
in
lysine
36
methylation
of
histone
H
3
and
a
decrease
in
lysine
27
methylation
across
the
genome
,
leading
to
a
more
open
structural
state
of
the
chromatin
.
Loss
of
MMSET
expression
alters
adhesion
properties
,
suppresses
growth
,
and
induces
apoptosis
in
MM
cells
.
Consequently
,
genes
affected
by
high
levels
of
MMSET
are
implicated
in
the
p
53
pathway
,
cell
cycle
regulation
,
and
integrin
signaling
.
Regulation
of
many
of
these
genes
required
functional
histone
methyl-transferase
activity
of
MMSET
.
These
results
implicate
MMSET
as
a
major
epigenetic
regulator
in
t
(
4
;
14
)
+
MM
.
Diseases
Validation
Diseases presenting
"functional histone"
symptom
wolf-hirschhorn syndrome
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