Induction NN B-NP
of IN B-PP
NF-KB NN B-NP
during IN B-PP
monocyte NN B-NP
differentiation NN I-NP
by IN B-PP
HIV NN B-NP
type NN I-NP
1 CD I-NP
infection NN I-NP
. . O

The DT B-NP
production NN I-NP
of IN B-PP
human JJ B-NP
immunodeficiency NN I-NP
virus NN I-NP
type NN I-NP
1 CD I-NP
( ( O
HIV-1 NN B-NP
) ) O
progeny NN B-NP
was VBD B-VP
followed VBN I-VP
in IN B-PP
the DT B-NP
U937 NN I-NP
promonocytic JJ I-NP
cell NN I-NP
line NN I-NP
after IN B-PP
stimulation NN B-NP
either CC B-PP
with IN I-PP
retinoic JJ B-NP
acid NN I-NP
or CC O
PMA NN B-NP
COMMA COMMA O
and CC O
in IN B-PP
purified VBN B-NP
human JJ I-NP
monocytes NNS B-NP
and CC O
macrophages NNS B-NP
. . O

Electrophoretic JJ B-NP
mobility NN I-NP
shift NN I-NP
assays NNS I-NP
and CC O
Southwestern NN B-NP
blotting NN I-NP
experiments NNS I-NP
were VBD B-VP
used VBN I-VP
to TO B-VP
detect VB I-VP
the DT B-NP
binding NN I-NP
of IN B-PP
cellular JJ B-NP
transactivation NN I-NP
factor NN I-NP
NF-KB NN I-NP
to TO B-PP
the DT B-NP
double JJ I-NP
repeat-KB JJ I-NP
enhancer NN I-NP
sequence NN I-NP
located JJ B-ADJP
in IN B-PP
the DT B-NP
long JJ I-NP
terminal JJ I-NP
repeat NN I-NP
. . O

PMA NN B-NP
treatment NN I-NP
COMMA COMMA O
and CC B-CONJP
not RB I-CONJP
retinoic JJ B-NP
acid NN I-NP
treatment NN I-NP
of IN B-PP
the DT B-NP
U937 NN I-NP
cells NNS I-NP
acts VBZ B-VP
in IN B-PP
inducing VBG B-VP
NF-KB NN B-NP
expression NN I-NP
in IN B-PP
the DT B-NP
nuclei NNS I-NP
. . O

In IN B-PP
nuclear JJ B-NP
extracts NNS I-NP
from IN B-PP
monocytes NNS B-NP
or CC O
macrophages NNS B-NP
COMMA COMMA O
induction NN B-NP
of IN B-PP
NF-KB NN B-NP
occurred VBD B-VP
only RB B-SBAR
if IN I-SBAR
the DT B-NP
cells NNS I-NP
were VBD B-VP
previously RB I-VP
infected VBN I-VP
with IN B-PP
HIV-1 NN B-NP
. . O

When WRB B-ADVP
U937 NN B-NP
cells NNS I-NP
were VBD B-VP
infected VBN I-VP
with IN B-PP
HIV-1 NN B-NP
COMMA COMMA O
no DT B-NP
induction NN I-NP
of IN B-PP
NF-KB NN B-NP
factor NN I-NP
was VBD B-VP
detected VBN I-VP
COMMA COMMA O
whereas IN O
high JJ B-NP
level NN I-NP
of IN B-PP
progeny NN B-NP
virions NNS I-NP
was VBD B-VP
produced VBN I-VP
COMMA COMMA O
suggesting VBG B-VP
that IN B-SBAR
this DT B-NP
factor NN I-NP
was VBD B-VP
not RB I-VP
required VBN I-VP
for IN B-PP
viral JJ B-NP
replication NN I-NP
. . O

These DT B-NP
results NNS I-NP
indicate VBP B-VP
that IN B-SBAR
in IN B-PP
monocytic JJ B-NP
cell NN I-NP
lineage NN I-NP
COMMA COMMA O
HIV-1 NN B-NP
could MD B-VP
mimic VB I-VP
some DT O
differentiation\/activation JJ B-NP
stimuli NNS B-NP
allowing VBG B-VP
nuclear JJ B-NP
NF-KB NN I-NP
expression NN I-NP
. . O

Positive JJ B-NP
and CC I-NP
negative JJ I-NP
regulation NN I-NP
of IN B-PP
immunoglobulin NN B-NP
gene NN I-NP
expression NN I-NP
by IN B-PP
a DT B-NP
novel JJ I-NP
B-cell-specific JJ I-NP
enhancer NN I-NP
element NN I-NP
. . O

A DT B-NP
new JJ I-NP
B-cell-specific JJ I-NP
enhancer NN I-NP
element NN I-NP
has VBZ B-VP
been VBN I-VP
identified VBN I-VP
3' JJ B-NP
of IN B-PP
E4 NN B-NP
and CC O
the DT B-NP
octamerlike JJ I-NP
motifs NNS I-NP
in IN B-PP
the DT B-NP
human JJ I-NP
immunoglobulin NN I-NP
heavy-chain NN I-NP
gene NN I-NP
enhancer NN I-NP
. . O

Tandem JJ B-NP
copies NNS I-NP
of IN B-PP
this DT B-NP
67-bp JJ I-NP
MnlI-AluI NN I-NP
fragment NN I-NP
COMMA COMMA O
when WRB B-ADVP
fused VBN B-VP
to TO B-PP
the DT B-NP
chloramphenicol JJ I-NP
acetyltransferase NN I-NP
gene NN I-NP
driven VBN B-VP
by IN B-PP
the DT B-NP
conalbumin JJ I-NP
promoter NN I-NP
COMMA COMMA O
stimulated VBD B-VP
transcription NN B-NP
in IN B-PP
B NN B-NP
cells NNS I-NP
but CC B-PP
not RB B-PP
in IN I-PP
Jurkat NN B-NP
T NN I-NP
cells NNS I-NP
or CC O
HeLa NN B-NP
cells NNS I-NP
. . O

Footprinting NN B-NP
analysis NN I-NP
revealed VBD B-VP
that IN B-SBAR
the DT B-NP
identical JJ I-NP
sequence NN I-NP
CCGAAACTGAAAAGG NN I-NP
COMMA COMMA O
designated VBN B-VP
E6 NN B-NP
COMMA COMMA O
was VBD B-VP
protected VBN I-VP
by IN B-PP
nuclear JJ B-NP
extracts NNS I-NP
from IN B-PP
B NN B-NP
cells NNS I-NP
COMMA COMMA O
T NN B-NP
cells NNS I-NP
COMMA COMMA O
or CC O
HeLa NN B-NP
cells NNS I-NP
. . O

Gel NN B-NP
mobility NN I-NP
shift NN I-NP
assays NNS I-NP
using VBG B-VP
a DT B-NP
synthetic JJ I-NP
E6 NN I-NP
motif NN I-NP
detected VBD B-VP
a DT B-NP
B-cell-specific JJ I-NP
complex NN I-NP
in IN B-PP
addition NN I-PP
to TO I-PP
a DT B-NP
ubiquitous JJ I-NP
band NN I-NP
found VBN B-VP
also RB B-PP
in IN I-PP
T NN B-NP
cells NNS I-NP
and CC O
HeLa NN B-NP
cells NNS I-NP
. . O

In IN B-PP
agreement NN I-PP
with IN I-PP
the DT B-NP
results NNS I-NP
of IN B-PP
gel NN B-NP
retardation NN I-NP
assays NNS I-NP
COMMA COMMA O
tandem JJ B-NP
copies NNS I-NP
of IN B-PP
the DT B-NP
E6 NN I-NP
motif NN I-NP
stimulated VBD B-VP
transcription NN B-NP
in IN B-PP
ARH77 NN B-NP
and CC O
Raji NN B-NP
cells NNS B-NP
but CC B-PP
not RB B-PP
in IN I-PP
Jurkat NN B-NP
or CC O
HeLa NN B-NP
cells NNS B-NP
. . O

Furthermore RB B-ADVP
COMMA COMMA O
a DT B-NP
mutant JJ I-NP
E6 NN I-NP
motif NN I-NP
lost VBD B-VP
both CC O
in FW B-NP
vitro FW I-NP
binding NN I-NP
activity NN I-NP
and CC B-PP
in FW B-NP
vivo FW I-NP
enhancer NN I-NP
activity NN I-NP
. . O

In IN B-PP
striking JJ B-NP
contrast NN I-NP
to TO B-PP
the DT B-NP
mouse NN I-NP
Ig NN I-NP
heavy-chain JJ I-NP
enhancer NN I-NP
COMMA COMMA O
in IN B-PP
which WDT B-NP
the DT B-NP
octamer NN I-NP
motif NN I-NP
acts VBZ B-VP
as IN B-PP
a DT B-NP
B-cell-specific JJ I-NP
enhancer NN I-NP
element NN I-NP
COMMA COMMA O
the DT B-NP
human JJ I-NP
enhancer NN I-NP
contains VBZ B-VP
an DT B-NP
octamerlike JJ I-NP
sequence NN I-NP
with IN B-PP
one CD B-NP
base NN I-NP
substitution NN I-NP
which WDT B-NP
bound VBD B-VP
octamer-binding JJ B-NP
proteins NNS I-NP
with IN B-PP
only RB B-NP
very RB I-NP
low JJ I-NP
affinity NN I-NP
and CC O
showed VBD B-VP
no DT B-NP
enhancer NN I-NP
activity NN I-NP
of IN B-PP
its PRP$ B-NP
own JJ I-NP
. . O

Interestingly RB B-ADVP
COMMA COMMA O
the DT B-NP
MnlI-AluI NN I-NP
fragment NN I-NP
could MD B-VP
suppress VB I-VP
the DT B-NP
basal-level JJ I-NP
activity NN I-NP
of IN B-PP
the DT B-NP
conalbumin JJ I-NP
promoter NN I-NP
in IN B-PP
both CC O
Jurkat NN B-NP
and CC O
HeLa NN B-NP
cells NNS B-NP
. . O

Moreover RB B-ADVP
COMMA COMMA O
simian JJ B-NP
virus NN I-NP
40 CD I-NP
enhancer NN I-NP
activity NN I-NP
was VBD B-VP
blocked VBN I-VP
by IN B-PP
the DT B-NP
MnlI-AluI NN I-NP
fragment NN I-NP
in IN B-PP
HeLa NN B-NP
cells NNS I-NP
but CC B-PP
not RB B-PP
in IN I-PP
B NN B-NP
cells NNS I-NP
. . O

Thus RB B-ADVP
COMMA COMMA O
the DT B-NP
novel JJ I-NP
enhancer NN I-NP
element NN I-NP
identified VBN B-VP
in IN B-PP
this DT B-NP
study NN I-NP
is VBZ B-VP
probably RB B-ADVP
a DT B-NP
target NN I-NP
site NN I-NP
for IN B-PP
both CC B-NP
positive JJ I-NP
and CC I-NP
negative JJ I-NP
factors NNS I-NP
. . O

The DT B-NP
NF NN I-NP
kappa NN I-NP
B NN I-NP
independent JJ I-NP
cis-acting JJ I-NP
sequences NNS I-NP
in IN B-PP
HIV-1 NN B-NP
LTR NN I-NP
responsive NN B-ADJP
to TO B-PP
T-cell NN B-NP
activation NN I-NP
. . O

The DT B-NP
rate NN I-NP
of IN B-PP
transcription NN B-NP
initiation NN I-NP
directed VBN B-VP
by IN B-PP
the DT B-NP
long JJ I-NP
terminal JJ I-NP
repeat NN I-NP
( ( O
LTR NN B-NP
) ) O
of IN B-PP
HIV-1 NN B-NP
increases VBZ B-VP
in IN B-PP
response NN I-PP
to TO I-PP
mitogenic JJ B-NP
stimuli NNS I-NP
of IN B-PP
T NN B-NP
cells NNS I-NP
. . O

Here RB B-ADVP
we PRP B-NP
show VBP B-VP
that IN B-SBAR
the DT B-NP
response NN I-NP
of IN B-PP
the DT B-NP
HIV-1 NN I-NP
LTR NN I-NP
may MD B-VP
be VB I-VP
governed VBN I-VP
by IN B-PP
two CD B-NP
independent JJ I-NP
sequences NNS I-NP
located JJ B-ADJP
5' JJ B-NP
to TO B-PP
the DT B-NP
site NN I-NP
of IN B-PP
transcription NN B-NP
initiation NN I-NP
sequences NNS I-NP
that WDT B-NP
bind VBP B-VP
either CC O
NFAT-1 NN B-NP
or CC O
NF NN B-NP
kappa NN I-NP
B NN I-NP
. . O

The DT B-NP
rate NN I-NP
of IN B-PP
LTR-directed JJ B-NP
gene NN I-NP
expression NN I-NP
increased VBD B-VP
in IN B-PP
response NN I-PP
to TO I-PP
treatment NN B-NP
with IN B-PP
either CC O
a DT B-NP
phorbol NN I-NP
ester NN I-NP
or CC O
tumor NN B-NP
necrosis NN I-NP
factor NN I-NP
alpha NN I-NP
if IN B-SBAR
either CC O
the DT O
NFAT-1 NN B-NP
or CC O
NF NN B-NP
kappa NN I-NP
B NN I-NP
binding NN B-NP
sites NNS I-NP
were VBD B-VP
deleted VBN I-VP
COMMA COMMA O
but CC O
failed VBD B-VP
to TO I-VP
respond VB I-VP
to TO B-PP
these DT B-NP
mitogenic JJ I-NP
stimuli NNS I-NP
if IN B-SBAR
both DT B-NP
sequences NNS I-NP
were VBD B-VP
absent JJ B-ADJP
. . O

The DT B-NP
HIV-1 NN I-NP
mutant JJ I-NP
virus NN I-NP
containing VBG B-VP
both CC O
NF NN B-NP
kappa NN I-NP
B NN I-NP
and CC O
NFAT-1 NN B-NP
deletion NN B-NP
was VBD B-VP
able JJ B-ADJP
to TO B-VP
replicate VB I-VP
although IN B-SBAR
at IN B-PP
a DT B-NP
much JJ I-NP
decreased VBN I-NP
growth NN I-NP
rate NN I-NP
COMMA COMMA O
while IN B-SBAR
the DT B-NP
deletion NN I-NP
of IN B-PP
NFAT-1 NN B-NP
alone RB B-ADVP
increased VBD B-VP
the DT B-NP
viral JJ I-NP
growth NN I-NP
rate NN I-NP
in IN B-PP
Jurkat NN B-NP
cells NNS I-NP
. . O

Neither CC O
deletion NN B-NP
of IN B-PP
NF NN B-NP
kappa NN I-NP
B NN I-NP
nor CC O
deletion NN B-NP
of IN B-PP
NFAT-1 NN B-NP
decreased VBD B-VP
activation NN B-NP
of IN B-PP
viral JJ B-NP
replication NN I-NP
by IN B-PP
phorbol NN B-NP
ester NN I-NP
. . O

Specific JJ B-NP
depletion NN I-NP
of IN B-PP
the DT B-NP
B-cell NN I-NP
population NN I-NP
induced VBN B-VP
by IN B-PP
aberrant JJ B-NP
expression NN I-NP
of IN B-PP
human JJ B-NP
interferon NN I-NP
regulatory JJ I-NP
factor NN I-NP
1 CD I-NP
gene NN I-NP
in IN B-PP
transgenic JJ B-NP
mice NNS I-NP
. . O

Interferons NNS B-NP
( ( O
IFNs NNS B-NP
) ) O
are VBP B-VP
well RB I-VP
known VBN I-VP
both CC O
as IN B-PP
antiviral JJ B-NP
proteins NNS I-NP
and CC B-PP
as IN B-PP
potent JJ B-NP
regulators NNS I-NP
of IN B-PP
cell NN B-NP
growth NN B-NP
and CC O
differentiation NN B-NP
. . O

In IN B-PP
fact NN B-NP
COMMA COMMA O
IFNs NNS B-NP
inhibit VBP B-VP
growth NN B-NP
of IN B-PP
various JJ B-NP
normal JJ I-NP
and CC I-NP
transformed VBN I-NP
cell NN I-NP
types NNS I-NP
. . O

Previously RB B-ADVP
COMMA COMMA O
a DT B-NP
nuclear JJ I-NP
factor NN I-NP
COMMA COMMA O
IRF-1 NN B-NP
( ( O
interferon NN B-NP
regulatory JJ I-NP
factor NN I-NP
1 CD I-NP
) ) O
COMMA COMMA O
which WDT B-NP
binds VBZ B-VP
to TO B-PP
type NN B-NP
I CD I-NP
IFN NN I-NP
and CC O
some DT B-NP
IFN-inducible JJ I-NP
gene NN I-NP
promoters NNS I-NP
COMMA COMMA O
was VBD B-VP
identified VBN I-VP
and CC O
cloned VBN B-VP
. . O

Since IN B-SBAR
the DT B-NP
IRF-1 NN I-NP
gene NN I-NP
is VBZ B-VP
both CC O
virus NN B-NP
and CC O
IFN NN B-NP
inducible JJ B-ADJP
COMMA COMMA O
an DT B-NP
intriguing JJ I-NP
issue NN I-NP
is VBZ B-VP
raised VBN I-VP
as IN B-PP
to TO I-PP
whether IN B-SBAR
the DT B-NP
IRF-1 NN I-NP
gene NN I-NP
is VBZ B-VP
functioning VBG I-VP
in IN B-PP
IFN-mediated JJ B-NP
regulation NN I-NP
of IN B-PP
cell NN B-NP
growth NN B-NP
and CC O
differentiation NN B-NP
. . O

In IN B-PP
this DT B-NP
study NN I-NP
COMMA COMMA O
we PRP B-NP
generated VBD B-VP
transgenic JJ B-NP
mice NNS I-NP
carrying VBG B-VP
the DT B-NP
human JJ I-NP
IRF-1 NN I-NP
gene NN I-NP
linked VBN B-VP
to TO B-PP
the DT B-NP
human JJ I-NP
immunoglobulin NN I-NP
heavy-chain JJ I-NP
enhancer NN I-NP
. . O

In IN B-PP
the DT B-NP
transgenic JJ I-NP
mice NNS I-NP
COMMA COMMA O
all PDT B-NP
the DT I-NP
lymphoid JJ I-NP
tissues NNS I-NP
examined VBN B-VP
showed VBD B-VP
a DT B-NP
dramatic JJ I-NP
reduction NN I-NP
in IN B-PP
the DT B-NP
number NN I-NP
of IN B-PP
B NN B-NP
lymphocytes NNS I-NP
( ( O
B NN B-NP
cells NNS I-NP
) ) O
. . O

Preparation NN B-NP
and CC O
analysis NN B-NP
of IN B-PP
bone NN B-NP
marrow NN I-NP
cells NNS I-NP
from IN B-PP
the DT B-NP
chimeric JJ I-NP
mice NNS I-NP
indicated VBD B-VP
that IN B-SBAR
the DT B-NP
bone NN I-NP
marrow NN I-NP
is VBZ B-VP
the DT B-NP
effective JJ I-NP
site NN I-NP
for IN B-PP
specific JJ B-NP
depletion NN I-NP
of IN B-PP
the DT B-NP
B-cell NN I-NP
population NN I-NP
. . O

In IN B-PP
fact NN B-NP
COMMA COMMA O
transgenic JJ B-NP
bone NN I-NP
marrow NN I-NP
cells NNS I-NP
cocultured VBN B-VP
with IN B-PP
a DT B-NP
bone NN I-NP
marrow-derived JJ I-NP
stromal JJ I-NP
cell NN I-NP
line NN I-NP
revealed VBD B-VP
an DT B-NP
altered JJ I-NP
B-cell NN I-NP
maturation NN I-NP
pattern NN I-NP
. . O

Identification NN B-NP
and CC O
cloning NN B-NP
of IN B-PP
TCF-1 NN B-NP
COMMA COMMA O
a DT B-NP
T NN I-NP
lymphocyte-specific JJ I-NP
transcription NN I-NP
factor NN I-NP
containing VBG B-VP
a DT B-NP
sequence-specific JJ I-NP
HMG NN I-NP
box NN I-NP
. . O

CD3-epsilon NN B-NP
expression NN I-NP
is VBZ B-VP
controlled VBN I-VP
by IN B-PP
a DT B-NP
downstream JJ I-NP
T NN I-NP
lymphocyte-specific JJ I-NP
enhancer NN I-NP
element NN I-NP
. . O

We PRP B-NP
report VBP B-VP
the DT B-NP
identification NN I-NP
of IN B-PP
a DT B-NP
T NN I-NP
cell-specific JJ I-NP
transcription NN I-NP
factor NN I-NP
COMMA COMMA O
TCF-1 NN B-NP
COMMA COMMA O
binding VBG B-VP
to TO B-PP
this DT B-NP
element NN I-NP
. . O

The DT B-NP
multimerized JJ I-NP
recognition NN I-NP
motif NN I-NP
of IN B-PP
TCF-1 NN B-NP
constituted VBD B-VP
a DT B-NP
T NN I-NP
cell-specific JJ I-NP
enhancer NN I-NP
. . O

Subsequent JJ B-NP
cloning NN I-NP
of IN B-PP
TCF-1 NN B-NP
identified VBD B-VP
three CD B-NP
splice NN I-NP
alternatives NNS I-NP
. . O

TCF-1 NN B-NP
contained VBD B-VP
a DT B-NP
single JJ I-NP
DNA-binding JJ I-NP
HMG NN I-NP
box NN I-NP
most RBS B-ADJP
closely RB I-ADJP
related JJ I-ADJP
to TO B-PP
similar JJ B-NP
boxes NNS I-NP
in IN B-PP
the DT B-NP
putative JJ I-NP
mammalian JJ I-NP
sex-determining JJ I-NP
gene NN I-NP
SRY NN I-NP
and CC B-PP
in IN B-PP
the DT B-NP
Schizosaccharomyces FW I-NP
pombe FW I-NP
Mc NN I-NP
mating NN I-NP
type NN I-NP
gene NN I-NP
. . O

TCF-1 NN B-ADVP
mRNA NN I-ADVP
was VBD B-VP
expressed VBN I-VP
uniquely RB B-ADVP
in IN B-PP
T NN B-NP
lymphocytes NNS I-NP
. . O