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Molecular and Cellular Biology, January 1999, p. 284-295, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Cux/CDP Homeoprotein Is a Component of NF-µNR and Represses
the Immunoglobulin Heavy Chain Intronic Enhancer by
Antagonizing the Bright Transcription Activator
Zhiyong
Wang,1,
Adrian
Goldstein,1
Rui-Ting
Zong,2
Danjun
Lin,2
Ellis J.
Neufeld,3
Richard H.
Scheuermann,1,* and
Philip W.
Tucker2
Department of Pathology and Laboratory of
Molecular Pathology, The University of Texas Southwestern Medical
Center, Dallas, Texas 75235-90721;
Department of Microbiology and Institute for Cellular & Molecular Biology, University of Texas at Austin, Austin, Texas
78712-10952; and
Division of Pediatric
Hematology/Oncology, Children's Hospital, Dana Farber Cancer
Institute and Harvard Medical School, Boston, Massachusetts
021153
Received 12 May 1998/Returned for modification 21 July
1998/Accepted 22 September 1998
Nuclear matrix attachment regions (MARs) flanking the
immunoglobulin heavy chain intronic enhancer (Eµ) are the targets of the negative regulator, NF-µNR, found in non-B and early pre-B cells.
Expression library screening with NF-µNR binding sites yielded a cDNA
clone encoding an alternatively spliced form of the Cux/CDP homeodomain
protein. Cux/CDP fulfills criteria required for NF-µNR identity. It
is expressed in non-B and early pre-B cells but not mature B cells. It
binds to NF-µNR binding sites within Eµ with appropriate
differential affinities. Antiserum specific for Cux/CDP recognizes a
polypeptide of the predicted size in affinity-purified NF-µNR
preparations and binds NF-µNR complexed with DNA. Cotransfection with
Cux/CDP represses the activity of Eµ via the MAR sequences in both B
and non-B cells. Cux/CDP antagonizes the effects of the Bright
transcription activator at both the DNA binding and functional levels.
We propose that Cux/CDP regulates cell-type-restricted, differentiation
stage-specific Eµ enhancer activity by interfering with the function
of nuclear matrix-bound transcription activators.
*
Corresponding author. Mailing address: Department of
Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd.,
Dallas, TX 75235-9072. Phone: (214) 648-4115. Fax: (214) 648-4070. E-mail: scheuerm{at}utsw.swmed.edu.

Present address: Howard Hughes Medical Institute, University of
California at San Diego, La Jolla, CA 92093-0648.
Molecular and Cellular Biology, January 1999, p. 284-295, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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