Regulation of expression of the type I collagen genes

Slack, James L.; Liska, DeAnn; Börnstein, Paul

doi:10.1002/ajmg.1320450203

Cited by 118 publications

(61 citation statements)

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“…Type I collagen, the most abundant mammalian collagen, consists of two ␣1(I) chains and one ␣2(I) chain that are coordinately expressed (1)(2)(3). Excessive deposition of type I collagen, characteristic of many fibrotic disorders (4), most likely results from transcriptional activation of collagen genes in response to cytokines and other factors present in prefibrotic/ inflammatory lesions.…”

mentioning

confidence: 99%

Oncostatin M Stimulates Transcription of the Human α2(I) Collagen Gene via the Sp1/Sp3-binding Site

Ihn

LeRoy

Trojanowska

1997

Journal of Biological Chemistry

138

125

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Oncostatin M (OSM), a member of the hematopoietic cytokine family, has been implicated in excessive bone growth and in the process of fibrosis. As part of an ongoing study of the molecular mechanisms of fibrosis, we have investigated the transcriptional regulation of the ␣2(I) collagen gene by OSM in human fibroblasts. An OSM response element was mapped by deletional analysis between base pairs (bp) ؊148 and ؊108 in the ␣2(I) collagen promoter. Further functional analysis of the ␣2(I) collagen promoter containing various substitution mutations revealed that both the basal activity and OSM stimulation of this promoter are mediated by a TCCTCC motif located between bp ؊128 and ؊123. Furthermore, three copies of the 12-bp synthetic ␣2(I) collagen promoter fragment containing the "TCC" motif conferred OSM inducibility to the otherwise unresponsive thymidine kinase promoter. Electrophoretic mobility shift assays demonstrated that the TCCTCC motif constitutes a novel binding site for the transcription factors Sp1 and Sp3. No differences have been observed in in vitro gel shift binding assays between unstimulated and OSMstimulated fibroblasts. However, subtle conformational changes were detected in the region of the promoter surrounding TCC repeats after OSM stimulation using in vivo footprint analysis. In conclusion, this study characterized a dual-function response element that mediates the basal activity and OSM stimulation of the human ␣2(I) collagen promoter.Type I collagen, the most abundant mammalian collagen, consists of two ␣1(I) chains and one ␣2(I) chain that are coordinately expressed (1-3). Excessive deposition of type I collagen, characteristic of many fibrotic disorders (4), most likely results from transcriptional activation of collagen genes in response to cytokines and other factors present in prefibrotic/ inflammatory lesions. The most widely studied cytokine involved in collagen deposition is TGF-␤ 1 ; nonetheless, other cytokines such as IL-4, IL-1, or OSM share many biological effects of TGF-␤ including stimulation of collagen synthesis and may play important roles in extracellular matrix accumulation during fibrotic process, especially immune-mediated fibrosis (5-7).OSM is produced by activated T cells (8) and monocytes (9) and belongs to a subfamily of hematopoietic cytokines that also includes IL-6, IL-11, LIF (leukemia inhibitory factor), and CNTF (ciliary neurotrophic factor). Members of this family bind receptor complexes containing a signal-transducing subunit termed gp130 (10 -12). Interestingly, OSM utilizes a dualreceptor system (13). First, a heterodimeric receptor complex consisting of gp130 and LIF receptor-␤ can be used by both OSM and LIF. A second heterodimeric receptor complex consisting of gp130 and OSM receptor-␤ is activated by OSM only. As a result, some of the biological effects are shared by OSM and LIF, whereas others are OSM-specific.In fibroblasts, OSM stimulates both collagen and glycosaminoglycan production (7). Moreover, OSM has been reported to stimulate the synthesis...

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confidence: 99%

Oncostatin M Stimulates Transcription of the Human α2(I) Collagen Gene via the Sp1/Sp3-binding Site

Ihn

LeRoy

Trojanowska

1997

Journal of Biological Chemistry

138

125

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“…A number of regulatory elements required for constitutive and inducible expressions have been identified in the promoter of both type I collagen genes (21,22). The previous studies have identified the ubiquitous factors, Sp1 and Sp3, and CBF/NF-Y and competitor (lane 1), and with nuclear extracts but without competitor (lanes 2 and 6).…”

Section: Discussionmentioning

confidence: 97%

“…Characterization of the cis-acting elements and trans-acting nuclear factors that modulate correct patterns of gene expression is necessary for understanding physiological and pathological conditions. Among the collagen genes, the transcriptional regulation of type I collagen has been most extensively studied, showing common features of the proximal promoter and tissue-specific enhancer (21,22). With regard to minor collagen, Penkov et al (23) identified the nuclear factors binding to the proximal promoter of COL5A2.…”

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confidence: 99%

The Transcription Factor CCAAT-binding Factor CBF/NF-Y and Two Repressors Regulate the Core Promoter of the Human Pro-α3(V) Collagen Gene (COL5A3)

Nagato

Matsuo²,

Sumiyoshi³

et al. 2004

Journal of Biological Chemistry

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To elucidate the mechanisms underlining ␣3(V) collagen chain expression, we performed an initial analysis of the structure and function of the core promoter of the human COL5A3 gene. The core promoter, which lacks a typical TATA motif and has a high GC content, was defined within the ؊129 bp immediately upstream from the major transcription start site by transient transfection experiments. In this region, we identified four DNAprotein complexes, named A, B, C, and D, by a combination of DNase I footprinting and electrophoretic mobility shift assays. Electrophoretic mobility shift assays using mutant oligonucleotide revealed that the complexes A, B, C, and D bind to ؊122 to ؊117, the ؊101 to ؊96, the ؊83 to ؊78, and the ؊68 to ؊57 bp, respectively. The competition assays using consensus oligonucleotides and supershift assays with specific antibodies Vertebrate collagens, a large family of extracellular proteins, are critically important for the formation and function of virtually every organ system (1). Among them, fibrillar collagen, which includes five different molecular types I, II, III, V, and XI, participates in the formation of fibrils with molecules packed in quarter-staggered arrays (2, 3). The fibrillar collagens are divided into major types (I-III) and minor types (V and XI) based on their relative expression levels. Minor fibrillar collagen types V and XI are incorporated into the fibrils of the much more abundant collagen types I and II, respectively, and act as regulators of the sizes and shapes of the resultant heterotypic fibrils (4 -7). The collagen molecules are either homotrimers with ␣ chains or heterotrimers with two or three different ␣ chains. The predominant molecular form of type V is the heterotrimer [␣1(V)] 2 ␣2(V) and is expressed in most tissues (8). Other forms of type V collagen include the [␣1(V)] 3 homotrimer that is synthesized in cultures of hamster lung cells (9) and the ␣1(V)␣2(V)␣3(V) heterotrimer that can be extracted from the placenta (10 -12). Cross-type heterotrimer composed of ␣2(V) and ␣1(XI) chains is present in the rhabdomyosarcoma cell line A204 and bovine vitreous (13,14). These findings suggest that type V and type XI chains constitute a single collagen type in which different combinations of chains associate in a tissue-specific manner. Recently, a fourth chain, ␣4(V), expressed in rat Schwann cells was reported (15). This ␣ chain, which can form molecules with ␣1(V) and ␣2(V) chains, seems to be the counterpart of the mouse and human ␣3(V) chain (16).Type V collagen, which is widely expressed spatially and temporally, is expressed in the mouse embryo as early as 11 days post-coitum (17). Altered production of type V collagen is associated with some connective tissue pathology, such as inflammation, some forms of cancer, and atherosclerosis (18 -20). Characterization of the cis-acting elements and trans-acting nuclear factors that modulate correct patterns of gene expression is necessary for understanding physiological and pathological conditions. Among the collag...

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“…Potential binding sites for AP2 havc been identified in the regulatory regions of the tnousc rrl(V1) (Bonaldo et al, 1993) and other collagcn genes (Slack et al, 1993), but actual binding of AP2 t o these sites has not heen demonstrated. 'The transcription factor AP2 is expressed in several embryonic tissues arid in the neural crest cell lineages during mouse embryogenesis (Mirchell el nl., 1991).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Human α1(VI) Collagen Promoter and its Comparison with Human α2(VI) Promoters

Saitta

Chu

1995

European Journal of Biochemistry

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From a hutniin costnid library, we isolaled a clone (93) with an insert of 32 kb, encoding thc aminotcrininal and the S-end flanking region of the rrl (VI) collagen gcnc. Exnn 1 was found to be lY4 bp and conlitin the S' untranslated region plus 97 bp coding sequencc. Exon 2 consists of 130 bp, ii size that is cnriscrved across the chicken and fnoilsc species. s 1 -nuclease-protection assays and pri mer-cxtension analysis, using tnRNA from human dermal fibroblasts, show the presence of multiple transcription slart sites located in a region of 220 nuclcolides. Canonical TATA und CAAT boxes, as found in the chickcn and mouse a1 promoters, wcre absent in the human cxl(V1) protnoler. The promoter region froni positions -1 to -190, is ii polypyriniidinelpolypurine-rich region containing 12 CCC?'CCCC (CT clement consensus) sequcnces and has multiple potential binding sites for the Spl and AP2 transcriptinn factors. These regulatory proteins bind to the u2(V1) promoters ISaitta, B. (HT1080) cell lines. The DNA constructs drive the expression of the chlorainphenicol acetyl triinsltrase (CAT) gene. The resulls show strong CAT activity for the constructs at positions -1700, -298 ant1 -257, while low activity was found for the constructs at positions -4400, -142 and -5 when transfected in fibroblasts. The expcrirnents also identified positivc and negative regulalory regions in the rxl(V1) promoter CAT constructs when transfected in fibroblasts, but did not identify thein in the fibrosarcoma cells.

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Regulation of expression of the type I collagen genes

Cited by 118 publications

References 119 publications

Oncostatin M Stimulates Transcription of the Human α2(I) Collagen Gene via the Sp1/Sp3-binding Site

Oncostatin M Stimulates Transcription of the Human α2(I) Collagen Gene via the Sp1/Sp3-binding Site

The Transcription Factor CCAAT-binding Factor CBF/NF-Y and Two Repressors Regulate the Core Promoter of the Human Pro-α3(V) Collagen Gene (COL5A3)

Characterization of the Human α1(VI) Collagen Promoter and its Comparison with Human α2(VI) Promoters

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