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A random Abstract
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Our Team
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
.
Diseases
Validation
Diseases presenting
"hodgkin lymphoma"
symptom
esophageal adenocarcinoma
hodgkin lymphoma, classical
monosomy 21
primary effusion lymphoma
severe combined immunodeficiency
systemic capillary leak syndrome
waldenström macroglobulinemia
This symptom has already been validated