Cell-specific expression of alpha 1(I) collagen-hGH minigenes in transgenic mice.

Liska, DeAnn; Reed, May J.; Sage, E. Helene; Börnstein, Paul

doi:10.1083/jcb.125.3.695

Cited by 69 publications

(68 citation statements)

References 39 publications

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“…In the above model, these sequences are assumed not to interact with the ACH, as they belong to a different functional transcription unit and can consequently synergize with local promoters. Consistent with this suggestion, unpublished work 3 has shown that the short intergenic region between Emilin1 and Khk contains an activating sequence for Khk that is located within the 16.8-kb fragment studied here.…”

Section: Discussionsupporting

confidence: 70%

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Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Fabbro

Gemmis

Braghetta

et al. 2005

Journal of Biological Chemistry

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The location of regions that regulate transcription of the murine Emilin1 gene was investigated in a DNA fragment of 16.8 kb, including the entire gene and about 8.7 and 0.6 kb of 5-and 3-flanking sequences, respectively. The 8.7-kb segment contains the 5-end of the putative 2310015E02Rik gene and the sequence that separates it from Emilin1, whereas the 0.6-kb fragment covers the region between Emilin1 and Ketohexokinase genes. Sequence comparison between species identified several conserved regions in the 5-flanking sequence. Most of them contained chromatin DNase I-hypersensitive sites, which were located at about ؊950 (HS1), ؊3100 (HS2), ؊4750 (HS3), and ؊5150 (HS4) in cells expressing Emilin1 mRNA. Emilin1 transcription initiates at multiple sites, the major of which correspond to two Initiator sequences. Promoter assays suggest that core promoter activity was mainly dependent on Initiator1 and on Sp1-binding sites close to the Initiators. Moreover, one important regulatory region was contained between ؊1 and ؊169 bp and a second one between ؊630 bp and ؊1.1 kb. The latter harbors a putative binding site for transcription factor AP1 matching the location of HS1. The function of different regions was studied by expressing lacZ constructs in transgenic mice. The results show that the 16.8-kb segment contains regulatory sequences driving high level transcription in all the tissues where Emilin1 is expressed. Moreover, the data suggest that transcription in different tissues is achieved through combinatorial cooperation between various regions, rather than being dependent on a single cis-activating region specific for each tissue.

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Section: Discussionsupporting

confidence: 70%

“…gated the regulatory sequences responsible for tissue-specific expression of ECM genes (1)(2)(3)(4)(5)(6). The overall picture coming from these studies is a modular arrangement of regulatory regions (mostly enhancers), meaning that each region is a distinct and independent regulator of transcription in a specific tissue or in a set of tissues.…”

mentioning

confidence: 99%

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Fabbro

Gemmis

Braghetta

et al. 2005

Journal of Biological Chemistry

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“…9 B), since collagen gene expression in dermal fibroblasts has been shown to require the first intron (23). However, expression of the -1627 COL-/3-galactosidase transgene was readily detected in tendon, indicating that the first intron is not required for collagen a I(I) gene expression in tendon fibroblasts (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The comparable values for the -440 COL-hGH and -2300 COL-hGH mRNAs in day 10 stellate cells, were 40.3 and 106, respectively. The variable baseline expression of the transgenes is related to copy number and "leakiness" of the construct, and it is therefore less informative than the increase in expression following activation, as described previously (23 CCAAT binding proteins are thought to be important in the regulation of the collagen a I(I) gene because in human, rat, and mouse two highly conserved CCAAT binding sequences are present in the collagen a I(I) promoter sequence ( 19). CBF is a CCAAT binding factor isolated from liver nuclear extracts which binds to both CCAAT sites (38).…”

Section: Resultsmentioning

confidence: 99%

“…In studies of transgenic animals the critical cis-acting element of the collagen al (I) gene has been located for skin and tail in the -2300 to -440-bp region (22,23), and for bone between -2296 and -1672 bp (24). Therefore, in these cell types with high levels of expression of the collagen al (I) gene, a key regulatory region excludes the -0.44-kb 5' region.…”

Section: Introductionmentioning

confidence: 99%

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Two different cis-acting regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts.

Houglum¹,

Buck²,

Alcorn³

et al. 1995

J. Clin. Invest.

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The expression of the collagen a,(I) gene in activated stellate cells plays an important role during liver fibrogenesis.To identify the critical cis-elements of the collagen al (I) gene in stellate cells, we used transgenic animals bearing various collagen al(I) regulatory regions directing the expression of either a human growth hormone minigene or the bacterial 8-galactosidase gene. We found that collagen aC (1)-human growth hormone transgene expression was constitutively high in tendon and skin, provided the transgene contained the -2.3 to -0.44 kb collagen regulatory region. However in the liver, expression was stimulated several-fold, as was the endogeneous gene, by the fibrogenic hepatotoxin carbon tetrachloride. This stimulation occurred whether the collagen 5' regulatory region extended -2.3, -1.6 or -0.44 kb, and in the presence or absence of much of the first intron (+292 to +1607 bp). In addition, the -0.44 kb 5' region was sufficient for high-level transgene expression in stellate cells, following their activation by culture on plastic. In contrast, in skin and tendon, high-level transcription of the collagen al(I) gene required the -2.3 to -0.44 kb 5' flanking region. Thus, two different cis-regulatory regions direct cell-specific transcription of the collagen a1 (I) gene in stellate cells and in skin and tendon. (J. Clin. Invest. 1995. 96:2269-2276

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Type I collagen-deficient Mov-13 mice do not retain SPARC in the extracellular matrix: Implications for fibroblast function

Iruela‐Arispe

Vernon

et al. 1996

Dev. Dyn.

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The Mou-13 strain of mice was created by the insertion of the murine Moloney leukemia virus into the first intron of the d (1) collagen gene. Consequently, Mou-13 embryos do not transcribe a1 (I) collagen mRNA and lack type I collagen protein in the extracellular matrix (ECM). Homozygotes die within 12-14 days of embryonic development, in part from the rupture of large blood vessels, and also exhibit deficiencies in hematopoesis and assembly of the ECM (Liihler et al. [ 19841 Cell 385974307). Several matricellular proteins, proteoglycans, and growth factors bind to type I collagen, e.g., fibronectin, secreted protein acidic and rich in cysteine (SPARC), decorin, and transforming growth factor+. Here we investigate the expression and function of SPARC in the absence of type I collagen. We show that fibroblasts isolated from Mou-13 homozygous, heterozygous, and wild-type embryos transcribed and translated SPARC mRNA in vitro. However, accumulation of extracellular SPARC was severely affected in the tissues of Mou-13 homozygotes, whereas extracellular deposition of the secreted glycoproteins fibronectin and type I11 collagen was not altered. Since SPARC has been shown to be a regulator of cell shape, the functional consequences of the absence of extracellular SPARC were evaluated in collagen gel contraction assays. Fibroblasts isolated from homozygous Mou-13 mice did not contract native type I collagen gels as efficiently as fibroblasts from heterozygous littermates; however, addition of exogenous SPARC enhanced the contraction of collagen by homozygous Mou-13 fibroblasts. The stirnulatory effect of SPARC was blocked by antibodies specific for the amino terminus of the protein. These results provide evidence that type I collagen is one of the major extracellular proteins that binds SPARC in vivo. Furthermore, the capacity of fibroblasts to contract ECM in vitro is enhanced by extracellular SPARC. W e therefore propose that the remodeling of ECM by cells in vivo is regulated in part by a specific interaction between SPARC and type I collagen. D IPPB Wiey-Liss, Inc.

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Cell-specific expression of alpha 1(I) collagen-hGH minigenes in transgenic mice.

Cited by 69 publications

References 39 publications

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Two different cis-acting regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts.

Type I collagen-deficient Mov-13 mice do not retain SPARC in the extracellular matrix: Implications for fibroblast function

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