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A random Abstract
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Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.
[hodgkin lymphoma, classical]
Deregulated
transcription
factor
(
TF
)
activities
are
commonly
observed
in
hematopoietic
malignancies
.
Understanding
tumorigenesis
therefore
requires
determining
the
function
and
hierarchical
role
of
individual
TFs
.
To
identify
TFs
central
to
lymphomagenesis
,
we
identified
lymphoma
type
-
specific
accessible
chromatin
by
global
mapping
of
DNaseI
hypersensitive
sites
and
analyzed
enriched
TF
-binding
motifs
in
these
regions
.
Applying
this
unbiased
approach
to
classical
Hodgkin
lymphoma
(
HL
)
,
a
common
B-
cell-derived
lymphoma
with
a
complex
pattern
of
deregulated
TFs
,
we
discovered
interferon
regulatory
factor
(
IRF
)
sites
among
the
top
enriched
motifs
.
High
-level
expression
of
the
proinflammatory
TF
IRF
5
was
specific
to
HL
cells
and
crucial
for
their
survival
.
Furthermore
,
IRF
5
initiated
a
regulatory
cascade
in
human
non-
Hodgkin
B-
cell
lines
and
primary
murine
B
cells
by
inducing
the
TF
AP
-
1
and
cooperating
with
NF-κB
to
activate
essential
characteristic
features
of
HL
.
Our
strategy
efficiently
identified
a
lymphoma
type
-
specific
key
regulator
and
uncovered
a
tumor
promoting
role
of
IRF
5
.