title: Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations.
abstract: Microphthalmia-associated transcription factor (Mitf) regulates the differentiation of melanocytes, optic cup-derived retinal pigment epithelium (RPE), and some types of bone marrow-derived cells. Mitf consists of at least five isoforms with different N-termini, each of which is encoded by a separate exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D, that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf mutations, but not expressed in other Mitf target cells, including melanocyte-lineage cells and natural killer cells. The initiation Met of MITF-D is located in the downstream domain (B1b domain) that is shared by other MITF isoforms. The 5'-untranslated region of MITF-D mRNA is encoded by the newly identified first exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with different expression patterns by using the alternative promoters in a cell-dependent manner, thereby providing the molecular basis for the phenotypic variability seen in the MITF/Mitf mutants.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Ken ichi
authors.initials: Ki
authors.lastname: Yasumoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Udono
authors.forename: Ken ichi
authors.initials: Ki
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Saito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D009154:Mutation; D010010:Osteoclasts / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors