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Promoter Mediated by Stat6 and C/EBPß
Tularik Inc., South San Francisco, CA 94080
Transcription of the Ig H chain germline transcripts is a
prerequisite for class switching. Expression of the 
germline
transcript is induced by IL-4 and requires the integrity of a composite
IL-4 response element. The element is bound by the IL-4-inducible
transcription factor Stat6 and one or more members of the
CAAT/enhancer-binding protein (C/EBP) family, a constitutively
expressed class of transcription factors. Here, we show that Stat6 and
C/EBPß cooperate to synergistically activate transcription from the
element. The effect was most pronounced in lymphoid cells, and the
activation domains of both proteins were required to achieve this
synergy. Although other members of the C/EBP family are able to bind
the element, very little cooperativity was seen with C/EBP
and none
with C/EBP
. In fact, C/EBP was able to inhibit IL-4-induced
reporter activity. Stat6 and C/EBPß bind the IL-4 response element
simultaneously. The fast dissociation rate apparent when Stat6 binds
this DNA element alone is slowed when C/EBPß binds at the neighboring
site. These data suggest a mechanism whereby C/EBPß stabilizes Stat6
binding at this element, thereby increasing the likelihood that both of
their activation domains will interact, possibly with other factors, to
activate transcription in an IL-4-dependent
manner.
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