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Mol Cell Biol, June 1998, p. 3223-3233, Vol. 18, No. 6
Department of Immunology, Duke University
Medical Center, Durham, North Carolina 27710
Received 6 January 1998/Returned for modification 20 February
1998/Accepted 9 March 1998
To understand the molecular basis for the dramatic functional
synergy between transcription factors that bind to the minimal T-cell
receptor
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Cooperation among Multiple Transcription Factors
Is Required for Access to Minimal T-Cell Receptor
-Enhancer
Chromatin In Vivo
enhancer (E
), we analyzed enhancer occupancy in
thymocytes of transgenic mice in vivo by genomic footprinting. We found
that the formation of a multiprotein complex on this enhancer in vivo
results from the occupancy of previously identified sites for CREB/ATF,
TCF/LEF, CBF/PEBP2, and Ets factors as well as from the occupancy of
two new sites 5' of the CRE site, GC-I (which binds Sp1 in vitro) and
GC-II. Significantly, although all sites are occupied on a wild-type
E
, all sites are unoccupied on versions of E
with mutations in
the TCF/LEF or Ets sites. Previous in vitro experiments demonstrated
hierarchical enhancer occupancy with independent binding of LEF-1 and
CREB. Our data indicate that the formation of a multiprotein complex on
the enhancer in vivo is highly cooperative and that no single E
binding factor can access chromatin in vivo to play a unique initiating
role in its assembly. Rather, the simultaneous availability of multiple enhancer binding proteins is required for chromatin disruption and
stable binding site occupancy as well as the activation of transcription and V(D)J recombination.
*
Corresponding author. Mailing address: Department of
Immunology, P.O. Box 3010, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-4985. Fax: (919) 684-8982. E-mail:
krang001{at}mc.duke.edu.
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