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Molecular and Cellular Biology, June 2007, p. 3911-3919, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.01455-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Microphthalmia Transcription Factor Isoforms in Mast Cells and the Heart{triangledown}

Sagi Tshori,1 Amir Sonnenblick,1 Nurit Yannay-Cohen,1 Gillian Kay,1 Hovav Nechushtan,2 and Ehud Razin1*

Department of Biochemistry, Hebrew University Medical School, Jerusalem, Israel,1 Department of Oncology, Hadassah Medical Center, Jerusalem, Israel2

Received 7 August 2006/ Returned for modification 9 October 2006/ Accepted 16 March 2007

The microphthalmia transcription factor (Mitf) is critical for the survival and differentiation of a variety of cell types. While on the transcript level it has been noted that melanocytes and cardiomyocytes express specific Mitf isoforms, mast cells express several isoforms, mainly Mitf-H and Mitf-MC, whose function has not been thoroughly investigated. We found that in mast cells the expression of the specific Mitf isoforms is dependent on physiological stimuli that cause a major shifting of promoter usage and internal splicing. For example, activation of the c-kit signaling pathway almost totally abolished one of the main splice isoforms. Since cardiomyocytes express only the Mitf-H isoform, they were an ideal system to determine this isoform's physiological role. We identified that the expression of myosin light-chain 1a (MLC-1a) is regulated by Mitf-H. Interestingly, the transactivation of MLC-1a by Mitf-H in cardiomyocytes is decreased by overexpression of the splice form with exon 6a. In conclusion, we found that there is physiological switching of Mitf isoforms and that the promoter context and the cell context have a combined influence on gene expression programs.


* Corresponding author. Mailing address: Department of Biochemistry, Hebrew University Medical School, P.O. Box 12272, Jerusalem 91120, Israel. Phone: 972 2 675 8288. Fax: 972 2 675 7379. E-mail: ehudr{at}cc.huji.ac.il

{triangledown} Published ahead of print on 16 April 2007.


Molecular and Cellular Biology, June 2007, p. 3911-3919, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.01455-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Carmi-Levy, I., Yannay-Cohen, N., Kay, G., Razin, E., Nechushtan, H. (2008). Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells. Mol. Cell. Biol. 28: 5777-5784 [Abstract] [Full Text]