Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells.

C. Reynaud, C. Gleyzal, Claude T Chapman, P. Sommer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The promoter activity of lysyl oxidase (LOX), the enzyme involved in collagen and elastin cross-linking and in tumor suppression, was compared in extracellular matrix producing cells and in tumorigenic c-Ha-ras-NIH-3T3 fibroblasts (RS485). The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts. Positive cis-acting elements were located around sites of transcription initiation in MFLC and SMC, but neither in RS485 fibroblasts nor in their non-transformed counterparts. The main positive cis-acting segment, at positions -808 to -585, was active in all cells, with the strongest activity in MFLC and SMC, and one segment, at positions -758 to -726, allowed the formation of one master DNA-protein complex with nuclear factors from all cells. The main inhibiting region, at positions -1,362 to -1,176, was active in all fibroblasts, but not in SMC, in an upstream position or in an enhancer/silencer position. This region carries two segments, called LOcoll and LOcol2 for their similarity to COL1A1 and COL1A2 promoter sequences, that were involved in the formation of a large multifactorial DNA complex with nuclear factors from all cells, though slightly for SMC. Another region, carrying a putative interferon response element (IRF) at positions -898 to -886, acted negatively on each type of cells. In conclusion, the LOX promoter is controlled by cross-talk between positive and negative cis-acting regions that are differentially active in various cells. The -758 to -726 region, with its putative C/EBP site, and the transcription initiation region are likely to play a master role in activating the LOX promoter in fibrocompetent MFLC and SMC. While the LOcol1/2 segment, with putative B-Myb binding sites, and the IRF carrying region, work negatively on the LOX promoter in transformed cells.

Original languageEnglish (US)
Pages (from-to)1237-1247
Number of pages11
JournalCellular and Molecular Biology
Volume45
Issue number8
StatePublished - Dec 1999
Externally publishedYes

Fingerprint

Protein-Lysine 6-Oxidase
Myofibroblasts
Fibroblasts
Smooth Muscle Myocytes
Muscle
Cells
Transcription Initiation Site
Elastin
DNA
Response Elements
Interferons
Tumors
Collagen
Binding Sites
Vascular Smooth Muscle
Enzymes
Extracellular Matrix

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells. / Reynaud, C.; Gleyzal, C.; Chapman, Claude T; Sommer, P.

In: Cellular and Molecular Biology, Vol. 45, No. 8, 12.1999, p. 1237-1247.

Research output: Contribution to journalArticle

@article{eaeb7cfca80945efb5dbb61792ccc115,
title = "Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells.",
abstract = "The promoter activity of lysyl oxidase (LOX), the enzyme involved in collagen and elastin cross-linking and in tumor suppression, was compared in extracellular matrix producing cells and in tumorigenic c-Ha-ras-NIH-3T3 fibroblasts (RS485). The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts. Positive cis-acting elements were located around sites of transcription initiation in MFLC and SMC, but neither in RS485 fibroblasts nor in their non-transformed counterparts. The main positive cis-acting segment, at positions -808 to -585, was active in all cells, with the strongest activity in MFLC and SMC, and one segment, at positions -758 to -726, allowed the formation of one master DNA-protein complex with nuclear factors from all cells. The main inhibiting region, at positions -1,362 to -1,176, was active in all fibroblasts, but not in SMC, in an upstream position or in an enhancer/silencer position. This region carries two segments, called LOcoll and LOcol2 for their similarity to COL1A1 and COL1A2 promoter sequences, that were involved in the formation of a large multifactorial DNA complex with nuclear factors from all cells, though slightly for SMC. Another region, carrying a putative interferon response element (IRF) at positions -898 to -886, acted negatively on each type of cells. In conclusion, the LOX promoter is controlled by cross-talk between positive and negative cis-acting regions that are differentially active in various cells. The -758 to -726 region, with its putative C/EBP site, and the transcription initiation region are likely to play a master role in activating the LOX promoter in fibrocompetent MFLC and SMC. While the LOcol1/2 segment, with putative B-Myb binding sites, and the IRF carrying region, work negatively on the LOX promoter in transformed cells.",
author = "C. Reynaud and C. Gleyzal and Chapman, {Claude T} and P. Sommer",
year = "1999",
month = "12",
language = "English (US)",
volume = "45",
pages = "1237--1247",
journal = "Cellular and Molecular Biology",
issn = "0145-5680",
publisher = "Cellular and Molecular Biology Association",
number = "8",

}

TY - JOUR

T1 - Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells.

AU - Reynaud, C.

AU - Gleyzal, C.

AU - Chapman, Claude T

AU - Sommer, P.

PY - 1999/12

Y1 - 1999/12

N2 - The promoter activity of lysyl oxidase (LOX), the enzyme involved in collagen and elastin cross-linking and in tumor suppression, was compared in extracellular matrix producing cells and in tumorigenic c-Ha-ras-NIH-3T3 fibroblasts (RS485). The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts. Positive cis-acting elements were located around sites of transcription initiation in MFLC and SMC, but neither in RS485 fibroblasts nor in their non-transformed counterparts. The main positive cis-acting segment, at positions -808 to -585, was active in all cells, with the strongest activity in MFLC and SMC, and one segment, at positions -758 to -726, allowed the formation of one master DNA-protein complex with nuclear factors from all cells. The main inhibiting region, at positions -1,362 to -1,176, was active in all fibroblasts, but not in SMC, in an upstream position or in an enhancer/silencer position. This region carries two segments, called LOcoll and LOcol2 for their similarity to COL1A1 and COL1A2 promoter sequences, that were involved in the formation of a large multifactorial DNA complex with nuclear factors from all cells, though slightly for SMC. Another region, carrying a putative interferon response element (IRF) at positions -898 to -886, acted negatively on each type of cells. In conclusion, the LOX promoter is controlled by cross-talk between positive and negative cis-acting regions that are differentially active in various cells. The -758 to -726 region, with its putative C/EBP site, and the transcription initiation region are likely to play a master role in activating the LOX promoter in fibrocompetent MFLC and SMC. While the LOcol1/2 segment, with putative B-Myb binding sites, and the IRF carrying region, work negatively on the LOX promoter in transformed cells.

AB - The promoter activity of lysyl oxidase (LOX), the enzyme involved in collagen and elastin cross-linking and in tumor suppression, was compared in extracellular matrix producing cells and in tumorigenic c-Ha-ras-NIH-3T3 fibroblasts (RS485). The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts. Positive cis-acting elements were located around sites of transcription initiation in MFLC and SMC, but neither in RS485 fibroblasts nor in their non-transformed counterparts. The main positive cis-acting segment, at positions -808 to -585, was active in all cells, with the strongest activity in MFLC and SMC, and one segment, at positions -758 to -726, allowed the formation of one master DNA-protein complex with nuclear factors from all cells. The main inhibiting region, at positions -1,362 to -1,176, was active in all fibroblasts, but not in SMC, in an upstream position or in an enhancer/silencer position. This region carries two segments, called LOcoll and LOcol2 for their similarity to COL1A1 and COL1A2 promoter sequences, that were involved in the formation of a large multifactorial DNA complex with nuclear factors from all cells, though slightly for SMC. Another region, carrying a putative interferon response element (IRF) at positions -898 to -886, acted negatively on each type of cells. In conclusion, the LOX promoter is controlled by cross-talk between positive and negative cis-acting regions that are differentially active in various cells. The -758 to -726 region, with its putative C/EBP site, and the transcription initiation region are likely to play a master role in activating the LOX promoter in fibrocompetent MFLC and SMC. While the LOcol1/2 segment, with putative B-Myb binding sites, and the IRF carrying region, work negatively on the LOX promoter in transformed cells.

UR - http://www.scopus.com/inward/record.url?scp=0033256229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033256229&partnerID=8YFLogxK

M3 - Article

C2 - 10643973

AN - SCOPUS:0033256229

VL - 45

SP - 1237

EP - 1247

JO - Cellular and Molecular Biology

JF - Cellular and Molecular Biology

SN - 0145-5680

IS - 8

ER -