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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that the expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi genotype, and demonstrated the involvement of MITF in the transcription of these genes. To obtain new genes whose transcription may be regulated by MITF, we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi CMCs, and recovered to nearly normal level by the overexpression of normal (+) MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in the Gr B and TPH promoters, respectively, and transactivated these two genes, indicating the involvement of +-MITF in their expression. Because TPH is the rate-limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+ and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the serotonin content in mi/mi CMCs.[1]

References

  1. Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells. Ito, A., Morii, E., Maeyama, K., Jippo, T., Kim, D.K., Lee, Y.M., Ogihara, H., Hashimoto, K., Kitamura, Y., Nojima, H. Blood (1998) [Pubmed]
 
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