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J Biol Chem, Vol. 274, Issue 51, 36159-36167, December 17, 1999
From the Department of Cell and Developmental Biology, Oregon
Health Sciences University, Portland, Oregon 97201
Tissue-specific expression of the
MRG1 Binds to the LIM Domain of Lhx2 and May Function as a
Coactivator to Stimulate Glycoprotein Hormone
-Subunit Gene
Expression*
and
-subunit
gene of glycoprotein hormones involves an enhancer element designated
the pituitary glycoprotein basal element, which interacts with the LIM
homeodomain transcription factor, Lhx2. In the present studies we have
explored the function of the LIM domain of Lhx2 in stimulating
-subunit transcription. When fused to the GAL4 DNA-binding domain,
the LIM domain of Lhx2 was shown to contain a transcriptional
activation domain. Furthermore, in the context of an -subunit
reporter gene in which a GAL4-binding site replaced the pituitary
glycoprotein basal element, the LIM domain enhanced both basal and
Ras-mediated transcription. In addition, a synergistic response to Ras
activation was observed when the Lhx2 LIM domain and the
transactivation domain of Elk1 are directed to a minimal reporter gene.
A yeast two-hybrid screen identified the recently described
melanocyte-specific gene-related gene 1 (MRG1) as an Lhx2
LIM-interacting protein. MRG1 was shown to bind Lhx2 in
vitro, and a co-immunoprecipitation assay provided evidence that
endogenous MRG1 forms a complex with Lhx2 in T3-1 cells. Expression
of MRG1 in T3-1 cells enhanced -subunit reporter gene activity.
MRG1 was also shown to bind in vitro to the TATA-binding
protein and the transcriptional coactivator, p300. These data suggest a
model in which the Lhx2 LIM domain activates transcription through
interaction with MRG1 leading to recruitment of p300/CBP and the
TATA-binding protein.
*
This work was supported in part by National Institutes of
Health Grant DK36407 (to R. M.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by an Oregon Health Sciences Foundation fellowship.
§
To whom correspondence should be addressed: Dept. of Cell and
Developmental Biology, Oregon Health Sciences University, 3181 S.W. Sam
Jackson Park Rd., Portland, OR 97201. Tel.: 503-494-7566; Fax:
503-494-4253; E-mail: maurerr@ohsu.edu.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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