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Originally published In Press as doi:10.1074/jbc.M203563200 on May 31, 2002
J. Biol. Chem., Vol. 277, Issue 34, 30901-30913, August 23, 2002
Identification of Glis1, a Novel Gli-related,
Krüppel-like Zinc Finger Protein Containing Transactivation and
Repressor Functions*
Yong-Sik
Kim,
Mark
Lewandoski ,
Alan O.
Perantoni§,
Shogo
Kurebayashi,
Gen
Nakanishi, and
Anton M.
Jetten¶
From the Cell Biology Section, Division of Intramural Research,
NIEHS, National Institutes of Health, Research Triangle Park, North
Carolina 27709 and the Laboratory of Cancer and
Developmental Biology and § Laboratory of Comparative
Carcinogenesis, NCI-Frederick, National Institutes of Health,
Frederick, Maryland 21702
In this study, we describe the identification and
characterization of a novel Krüppel-like protein named
Gli-similar 1 (Glis1). The Glis1 gene encodes an 84.3-kDa
proline-rich protein. Its five tandem zinc finger motifs exhibit
highest homology with those of members of the Gli and Zic subfamilies
of Krüppel-like proteins. Glis1 was mapped to mouse
chromosome 4C6. Northern blot analysis showed that expression of the
3.3-kb Glis1 mRNA is most abundant in placenta and adult kidney and
expressed at lower levels in testis. Whole mount in situ
hybridization on mouse embryos demonstrated that Glis1 is expressed in
a temporal and spatial manner during development; expression was most
prominent in several defined structures of mesodermal lineage,
including craniofacial regions, branchial arches, somites, vibrissal
and hair follicles, limb buds, and myotomes. Confocal microscopic
analysis showed that Glis1 is localized to the nucleus. The zinc finger
region plays an important role in the nuclear localization of Glis1.
Electrophoretic mobility shift assays demonstrated that Glis1 is able
to bind oligonucleotides containing the Gli-binding site consensus
sequence GACCACCCAC. Although monohybrid analysis showed that in
several cell types Glis1 was unable to induce transcription of a
reporter, deletion mutant analysis revealed the presence of a strong
activation function at the carboxyl terminus of Glis1. The
activation through this activation function was totally suppressed by a
repressor domain at its amino terminus. Constitutively active
Ca2+-dependent calmodulin kinase IV enhanced
Glis1-mediated transcriptional activation about 4-fold and may be
mediated by phosphorylation/activation of a co-activator. Our results
suggest that Glis1 may play a critical role in the control of gene
expression during specific stages of embryonic development.
*
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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF486579.
¶
To whom correspondence should be addressed. Tel.:
919-541-2768; Fax: 919-541-4133; E-mail: jetten@niehs.nih.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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