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| Subject Categories: Chromatin & Transcription | Development |
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| The EMBO Journal
(2002) 21, 2703–2714, doi: 10.1093/emboj/21.11.2703 |
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| Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling |
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| Ken-ichi Yasumoto, Kazuhisa Takeda, Hideo Saito, Ken-ichi Watanabe, Kazuhiro Takahashi and Shigeki Shibahara |
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Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan To whom correspondence should be addressed Shigeki Shibahara, shibahar@mail.cc.tohoku.ac.jp Received 19 March 2001; Revised 18 February 2002; Accepted 27 March 2002. |
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| Abstract |
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Wnt signals regulate differentiation of neural crest cells through the  -catenin associated with a nuclear mediator of the lymphoid-enhancing factor 1 (LEF-1)/T-cell factors (TCFs) family. Here we show the interaction between the basic helix−loop−helix and leucine-zipper region of microphthalmia-associated transcription factor (MITF) and LEF-1. MITF is essential for melanocyte differentiation and its heterozygous mutations cause auditory−pigmentary syndromes. Functional cooperation of MITF with LEF-1 results in synergistic transactivation of the dopachrome tautomerase (DCT) gene promoter, an early melanoblast marker. This activation depends on the separate cis-acting elements, which are also responsible for the induction of the DCT promoter by lithium chloride that mimics Wnt signaling. -catenin is required for efficient transactivation, but dispensable for the interaction between MITF and LEF-1. The interaction with MITF is unique to LEF-1 and not detectable with TCF-1. LEF-1 also cooperates with the MITF-related proteins, such as TFE3, to transactivate the DCT promoter. This study therefore suggests that the MITF/TFE3 family is a new class of nuclear modulators for LEF-1, which may ensure efficient propagation of Wnt signals in many types of cells. |
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| Keywords: dopachrome tautomerase, LEF-1, melanocyte, MITF, Wnt |
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