| RRC ID |
41560
|
| 著者 |
Watanabe K, Takeda K, Yasumoto K, Udono T, Saito H, Ikeda K, Takasaka T, Takahashi K, Kobayashi T, Tachibana M, Shibahara S.
|
| タイトル |
Identification of a distal enhancer for the melanocyte-specific promoter of the MITF gene.
|
| ジャーナル |
Pigment Cell Res
|
| Abstract |
Waardenburg syndrome (WS) is characterized by deafness and hypopigmentation because of the lack of melanocytes in the inner ear and skin. WS type 2 is associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF) that is required for melanocyte differentiation. MITF consists of multiple isoforms with different N-termini, one of which is exclusively expressed in melanocytes, named MITF-M. Its N-terminus is encoded by exon 1M that is under the regulation of the melanocyte-specific (M) promoter. Here we identify a distal regulatory region of 298 bp, located 14.5 kb upstream from exon 1M, which enhances the M promoter activity in cultured melanoma cells. This enhancer activity depends on the proximal M promoter region (-120 to -46). The MITF-M distal enhancer (MDE), thus identified, contains the binding sites for SOX10, a transcription factor responsible for another type of WS, known as Waardenburg-Hirschsprung syndrome. Characterization of MDE has suggested SOX10 as one of factors that are involved in the function of MDE. A putative MDE counterpart is located 12 kb upstream from mouse exon 1M and its role is discussed in relevance to the pathogenesis of red-eyed white Mitf mi-rw mice that exhibit small red eyes and white coat. Moreover, by in situ hybridization analysis, we suggest that Sox10 and Mitf-M (mRNA) are expressed in melanoblasts migrating toward the otic vesicle (prospective inner ear) of mouse embryos but are separately expressed in different cell types of the newborn cochlea. Thus, SOX10 regulates transcription from the M promoter in a developmental stage-specific manner.
|
| 巻・号 |
15(3)
|
| ページ |
201-11
|
| 公開日 |
2002-6-1
|
| DOI |
10.1034/j.1600-0749.2002.01080.x
|
| PII |
1o080
|
| PMID |
12028584
|
| MeSH |
Animals
Base Sequence
COS Cells
Cells, Cultured
Cochlea / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Enhancer Elements, Genetic
Gene Deletion
Genes, Reporter
HeLa Cells
High Mobility Group Proteins / metabolism
Humans
In Situ Hybridization
Luciferases / metabolism
Melanocytes / metabolism*
Mice
Mice, Inbred BALB C
Microphthalmia-Associated Transcription Factor
Molecular Sequence Data
Mutation
Neural Crest / metabolism
Plasmids / metabolism
Promoter Regions, Genetic
RNA, Messenger / metabolism
SOXE Transcription Factors
Sequence Homology, Nucleic Acid
Time Factors
Transcription Factors / genetics*
Transcription Factors / metabolism
Transfection
Waardenburg Syndrome / genetics
|
| 引用数 |
50
|
|
WOS 分野
|
DERMATOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HMV-II(RCB0777) |
