Little is known about mechanisms regulating gene expression for the α chains of basement membrane type IV collagen, arranged head-to-head in transcription units COL4A1-COL4A2, COL4A3-COL4A4, and COL4A5-COL4A6, and implicated broadly in genetic diseases. To investigate these mechanisms, we generated transgenic mouse lines bearing 5′-flanking sequences of COL4A5 and COL4A6, cloned upstream of a lacZ reporter gene. A 3.8-kb fragment upstream of COL4A6 directs reporter gene expression in the esophagus, stomach, and duodenum, whereas a 13.8-kb fragment directs expression in the esophagus only. A 10.6-kb fragment upstream of COL4A5 directs expression in the esophagus. Coupled with evidence of long-range conservation between human and mouse non-coding sequences, described herein, our findings provide the first indication that highly specialized patterns characteristic of COL4A5-COL4A6 expression in vivo arise from effects of distributed cis-acting regulatory elements on a bidirectional proximal promoter, itself transcriptionally competent.
|Original language||English (US)|
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Nov 14 2003|
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health grants to J. Zhou and Y. Segal. We thank Drs. Jacques Peschon, Joshua Sanes, and Jeffrey Miner for reagents, Stefan Kren for assistance with computational analysis, and Drs. Samuel Ho and Clifford Kashtan for critical reading of the manuscript.
- Collagen type IV
- Gastric mucosa
- Gene expression regulation
- Intestinal mucosa
- Mice, transgenic
- Nephritis, hereditary