The Nuclear LIM Domain Interactor NLI Mediates Homo- and Heterodimerization of LIM Domain Transcription Factors*
- From the ‡Biomedical Sciences Graduate Program and the**Department of Medicine, University of California at San Diego, La Jolla, California 92093-0650 and the ¶Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037
Abstract
LIM domain-containing transcription factors are required for embryonic survival and for the determination of many cell types. The combinatorial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and Lhx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innervation targets, implying a functional role for LIM homeodomain protein combinations in the specification of neuronal identity. NLI is a widely expressed, dimeric protein that has been shown to specifically interact with the LIM domains of LIM domain-containing transcription factors. The present studies demonstrate that NLI mediates homo- and heteromeric complex formation between LIM domain transcription factors, requiring both the N-terminal dimerization and C-terminal LIM interaction domains of NLI. Although the interaction between most LIM homeodomain proteins is dependent on NLI, a direct interaction between the LIM domains of Lhx3 and the homeodomains of Isl1 and Isl2 was also observed. This interaction was disrupted by NLI, demonstrating that the conformational state of Lhx3-Isl1/Isl2 complexes is modified by NLI. Evidence indicating that NLI facilitates long range enhancer-promoter interactions suggests that NLI-dependent LIM domain transcription factor complexes are involved in communication between transcriptional control elements.
Footnotes
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↵* This work was supported by National Institutes of Health Grant DK 13149 (to G. N. G.).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.
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↵§ Supported by National Institutes of Health Training Grant DK 07541.
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↵‖ Supported by the McKnight Foundation with startup funds for establishment of the laboratory provided by the Drown and Hoag Foundations.
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↵‡ To whom correspondence should be addressed: Dept. of Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0650. Tel.: 619-534-4310; Fax: 619-534-8193; E-mail: ggill{at}ucsd.edu.
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↵1 The abbreviations used are: LMO, LIM-only; HA, hemagglutinin; IP, immunoprecipitation; PAGE, polyacrylamide gel electrophoresis; LID, LIM interaction domain; MMCm, medial subdivision of the median motor column.
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↵2 L. W. Jurata, unpublished observations.
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↵3 S. L. Pfaff, unpublished observations.
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↵4 J. Thomas and S. Thor, personal communication.
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- Received September 29, 1997.
- Revision received December 9, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
