| Autor: |
Rim, Jong S., Atta, Mohamed G., Dahl, Stephen C., Berry, Gerard T., Handler, Joseph S., Kwon, H. Moo |
| Zdroj: |
Journal of Biological Chemistry; August 1998, Vol. 273 Issue: 32 p20615-20621, 7p |
| Abstrakt: |
The sodium/myo-inositol cotransporter is a plasma membrane protein responsible for concentrative cellular accumulation of myo-inositol in a variety of tissues. When cells in kidney and brain are exposed to a hyperosmolar salt condition (hypertonicity) due to the operation of urinary concentration mechanism and pathological conditions, respectively, they survive the stress of hypertonicity by raising the cellular concentration ofmyo-inositol. Transcription of the sodium/myo-inositol cotransporter gene is markedly stimulated in response to hypertonicity, leading to an increase in the activity of the cotransporter, which in turn drives the osmoprotective accumulation of myo-inositol. To understand the molecular mechanisms by which hypertonicity stimulates transcription, we analyzed the 5′-flanking region of the cotransporter gene forcis-acting regulatory sequences. We identified five tonicity-responsive enhancers that are scattered over 50 kilobase pairs. All the enhancers are variations of the same type of enhancer interacting with the transcription factor named tonicity-responsive enhancer binding protein. In vivomethylation experiments demonstrated that exposure of cells to hypertonicity increases the binding of tonicity-responsive enhancer binding protein to the enhancer sites, indicating that all of these enhancers are involved in the transcriptional stimulation. We conclude that the sodium/myo-inositol cotransporter gene is regulated by a large region (∼50 kilobase pairs) upstream of the gene. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
