Regulation of COL1A1 expression in type I collagen producing tissues: Identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice

A. Bedalov, Roberto Salvatori, M. Dodig, M. S. Kronenberg, B. Kapural, Z. Bogdanovic, B. E. Kream, C. O. Woody, S. H. Clark, K. Mack, D. W. Rowe, A. C. Lichtler

Research output: Contribution to journalArticle

Abstract

Previous deletion studies using a series of COL1A1-CAT fusion genes have indicated that the 625 bp region of the COL1A1 upstream promoter between - 2295 and -1670 bp is required for high levels of expression in bone, tendon, and skin of transgenic mice. To further define the important sequences within this region, a new series of deletion constructs extending to -1997, -1794, - 1763, and -1719 bp has been analyzed in transgenic mice. Transgene activity, determined by measuring CAT activity in tissue extracts of 6- to 8-day-old transgenic mouse calvariae, remains high for all the new deletion constructs and drops to undetectable levels in calvariae containing the -1670 bp construct. These results indicate that the 49 bp region of the COL1A1 promoter between -1719 and -1670 bp is required for high COL1A1 expression in bone. Although deletion of the same region caused a substantial reduction of promoter activity in tail tendon, the construct extending to -1670 bp is still expressed in this tissue. However, further deletion of the promoter to -944 bp abolished activity in tendon. Gel mobility shift studies identified a protein in calvarial nuclear extracts that is not found in tendon nuclear extracts, which binds within this 49 bp region. Our study has delineated sequences in the COL1A1 promoter required for expression of the COL1A1 gene in high type I collagen-producing tissues, and suggests that different cis elements control expression of the COL1A1 gene in bone and tendon.

Original languageEnglish (US)
Pages (from-to)1443-1451
Number of pages9
JournalJournal of Bone and Mineral Research
Volume10
Issue number10
StatePublished - 1995
Externally publishedYes

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Collagen Type I
Transgenes
Base Pairing
Tendons
Transgenic Mice
Bone and Bones
Skull
Gene Expression
Tissue Extracts
Gene Fusion
Genetic Promoter Regions
Tail
Gels
Skin
Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

Regulation of COL1A1 expression in type I collagen producing tissues : Identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice. / Bedalov, A.; Salvatori, Roberto; Dodig, M.; Kronenberg, M. S.; Kapural, B.; Bogdanovic, Z.; Kream, B. E.; Woody, C. O.; Clark, S. H.; Mack, K.; Rowe, D. W.; Lichtler, A. C.

In: Journal of Bone and Mineral Research, Vol. 10, No. 10, 1995, p. 1443-1451.

Research output: Contribution to journalArticle

Bedalov, A, Salvatori, R, Dodig, M, Kronenberg, MS, Kapural, B, Bogdanovic, Z, Kream, BE, Woody, CO, Clark, SH, Mack, K, Rowe, DW & Lichtler, AC 1995, 'Regulation of COL1A1 expression in type I collagen producing tissues: Identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice', Journal of Bone and Mineral Research, vol. 10, no. 10, pp. 1443-1451.
Bedalov, A. ; Salvatori, Roberto ; Dodig, M. ; Kronenberg, M. S. ; Kapural, B. ; Bogdanovic, Z. ; Kream, B. E. ; Woody, C. O. ; Clark, S. H. ; Mack, K. ; Rowe, D. W. ; Lichtler, A. C. / Regulation of COL1A1 expression in type I collagen producing tissues : Identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice. In: Journal of Bone and Mineral Research. 1995 ; Vol. 10, No. 10. pp. 1443-1451.
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abstract = "Previous deletion studies using a series of COL1A1-CAT fusion genes have indicated that the 625 bp region of the COL1A1 upstream promoter between - 2295 and -1670 bp is required for high levels of expression in bone, tendon, and skin of transgenic mice. To further define the important sequences within this region, a new series of deletion constructs extending to -1997, -1794, - 1763, and -1719 bp has been analyzed in transgenic mice. Transgene activity, determined by measuring CAT activity in tissue extracts of 6- to 8-day-old transgenic mouse calvariae, remains high for all the new deletion constructs and drops to undetectable levels in calvariae containing the -1670 bp construct. These results indicate that the 49 bp region of the COL1A1 promoter between -1719 and -1670 bp is required for high COL1A1 expression in bone. Although deletion of the same region caused a substantial reduction of promoter activity in tail tendon, the construct extending to -1670 bp is still expressed in this tissue. However, further deletion of the promoter to -944 bp abolished activity in tendon. Gel mobility shift studies identified a protein in calvarial nuclear extracts that is not found in tendon nuclear extracts, which binds within this 49 bp region. Our study has delineated sequences in the COL1A1 promoter required for expression of the COL1A1 gene in high type I collagen-producing tissues, and suggests that different cis elements control expression of the COL1A1 gene in bone and tendon.",
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AU - Dodig, M.

AU - Kronenberg, M. S.

AU - Kapural, B.

AU - Bogdanovic, Z.

AU - Kream, B. E.

AU - Woody, C. O.

AU - Clark, S. H.

AU - Mack, K.

AU - Rowe, D. W.

AU - Lichtler, A. C.

PY - 1995

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