Tissue- and developmental stage-specific activation of alpha 5 and alpha 6(IV) collagen expression in the upper gastrointestinal tract of transgenic mice.
Little is known about mechanisms regulating gene expression for the alpha 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.
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Christine
C
Herzog
Liyan
L
Zhuang
Lucian
L
Gorgan
Yoav
Y
Segal
Jing
J
Zhou
D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005809:Genes, Regulator; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D021122:Protein Subunits / Q000737:chemistry; D017385:Sequence Homology; D013045:Species Specificity; D014018:Tissue Distribution; D015533:Transcriptional Activation / Q000502:physiology*; D041742:Upper Gastrointestinal Tract / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
C478159:COL4A5 protein, human; D024141:Collagen Type IV; D021122:Protein Subunits