Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein

T. H. Lee, L. Klampfer, T. B. Shows, J. Vilcek

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

TSG6 was originally identified as a tumor necrosis factor (TNF)-inducible gene in human fibroblasts. Earlier we showed that the secretory TSG6 protein is a member of a family of hyaluronan-binding proteins that includes cartilage link protein, proteoglycan core protein, and the adhesion receptor CD44. In the present study we have used Southern blot analysis to demonstrate that TSG6 is a single-copy gene in the human and murine species. With the aid of a somatic cell hybrid mapping panel, TSG6 was assigned to human chromosome 2. Nuclear run-on analysis revealed that TNF produced a rapid, primary transcriptional activation of the TSG6 gene in normal human FS-4 fibroblasts. In order to learn more about the regulation of TSG6 gene expression, we cloned the TSG6 gene from a genomic library of human white blood cells. Sequencing of a 1.3-kilobase fragment of the 5'-flanking region of the TSG6 gene identified TATA-like and CAAT sequences near the transcription start site. In addition, potential binding sites for NF-IL-6, AP-1, interferon regulatory factors (IRF)-1 and -2, and glucocorticoid response elements were identified in the 5'-flanking region. A single transcription start site was identified by primer extension. Deletion analysis of the 5'-flanking region of the TSG6 DNA linked to the chloramphenicol acetyltransferase reporter gene revealed that a construct containing TSG6 DNA from positions -165 to +78 could be transcriptionally activated by interleukin(IL)-1, and to a lesser extent by TNF, upon transfection into FS-4 fibroblasts. The region that imparts inducibility by IL-1 or TNF (positions -165 to -58) contains potential binding sites for IRF-1 and -2, AP-1, and NF-IL-6. A region mediating transcriptional silencing was localized further upstream (between positions -332 and -165). The results suggest that TSG6 gene expression is regulated by an interplay of positively and negatively acting transactivating factors.

Original languageEnglish
Pages (from-to)6154-6160
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number9
Publication statusPublished - 1993 Jan 1

Fingerprint

CD44 Antigens
Interleukin-1
Tumor Necrosis Factor-alpha
Genes
Interferon Regulatory Factor-2
5' Flanking Region
Interferon Regulatory Factor-1
Fibroblasts
Transcription Initiation Site
Transcription Factor AP-1
Interleukin-6
Gene expression
Binding Sites
Chloramphenicol O-Acetyltransferase
Chromosomes, Human, Pair 2
Genomic Library
Hybrid Cells
DNA
Gene Expression Regulation
Human Chromosomes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein",
abstract = "TSG6 was originally identified as a tumor necrosis factor (TNF)-inducible gene in human fibroblasts. Earlier we showed that the secretory TSG6 protein is a member of a family of hyaluronan-binding proteins that includes cartilage link protein, proteoglycan core protein, and the adhesion receptor CD44. In the present study we have used Southern blot analysis to demonstrate that TSG6 is a single-copy gene in the human and murine species. With the aid of a somatic cell hybrid mapping panel, TSG6 was assigned to human chromosome 2. Nuclear run-on analysis revealed that TNF produced a rapid, primary transcriptional activation of the TSG6 gene in normal human FS-4 fibroblasts. In order to learn more about the regulation of TSG6 gene expression, we cloned the TSG6 gene from a genomic library of human white blood cells. Sequencing of a 1.3-kilobase fragment of the 5'-flanking region of the TSG6 gene identified TATA-like and CAAT sequences near the transcription start site. In addition, potential binding sites for NF-IL-6, AP-1, interferon regulatory factors (IRF)-1 and -2, and glucocorticoid response elements were identified in the 5'-flanking region. A single transcription start site was identified by primer extension. Deletion analysis of the 5'-flanking region of the TSG6 DNA linked to the chloramphenicol acetyltransferase reporter gene revealed that a construct containing TSG6 DNA from positions -165 to +78 could be transcriptionally activated by interleukin(IL)-1, and to a lesser extent by TNF, upon transfection into FS-4 fibroblasts. The region that imparts inducibility by IL-1 or TNF (positions -165 to -58) contains potential binding sites for IRF-1 and -2, AP-1, and NF-IL-6. A region mediating transcriptional silencing was localized further upstream (between positions -332 and -165). The results suggest that TSG6 gene expression is regulated by an interplay of positively and negatively acting transactivating factors.",
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Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein. / Lee, T. H.; Klampfer, L.; Shows, T. B.; Vilcek, J.

In: Journal of Biological Chemistry, Vol. 268, No. 9, 01.01.1993, p. 6154-6160.

Research output: Contribution to journalArticle

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T1 - Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein

AU - Lee, T. H.

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AU - Shows, T. B.

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N2 - TSG6 was originally identified as a tumor necrosis factor (TNF)-inducible gene in human fibroblasts. Earlier we showed that the secretory TSG6 protein is a member of a family of hyaluronan-binding proteins that includes cartilage link protein, proteoglycan core protein, and the adhesion receptor CD44. In the present study we have used Southern blot analysis to demonstrate that TSG6 is a single-copy gene in the human and murine species. With the aid of a somatic cell hybrid mapping panel, TSG6 was assigned to human chromosome 2. Nuclear run-on analysis revealed that TNF produced a rapid, primary transcriptional activation of the TSG6 gene in normal human FS-4 fibroblasts. In order to learn more about the regulation of TSG6 gene expression, we cloned the TSG6 gene from a genomic library of human white blood cells. Sequencing of a 1.3-kilobase fragment of the 5'-flanking region of the TSG6 gene identified TATA-like and CAAT sequences near the transcription start site. In addition, potential binding sites for NF-IL-6, AP-1, interferon regulatory factors (IRF)-1 and -2, and glucocorticoid response elements were identified in the 5'-flanking region. A single transcription start site was identified by primer extension. Deletion analysis of the 5'-flanking region of the TSG6 DNA linked to the chloramphenicol acetyltransferase reporter gene revealed that a construct containing TSG6 DNA from positions -165 to +78 could be transcriptionally activated by interleukin(IL)-1, and to a lesser extent by TNF, upon transfection into FS-4 fibroblasts. The region that imparts inducibility by IL-1 or TNF (positions -165 to -58) contains potential binding sites for IRF-1 and -2, AP-1, and NF-IL-6. A region mediating transcriptional silencing was localized further upstream (between positions -332 and -165). The results suggest that TSG6 gene expression is regulated by an interplay of positively and negatively acting transactivating factors.

AB - TSG6 was originally identified as a tumor necrosis factor (TNF)-inducible gene in human fibroblasts. Earlier we showed that the secretory TSG6 protein is a member of a family of hyaluronan-binding proteins that includes cartilage link protein, proteoglycan core protein, and the adhesion receptor CD44. In the present study we have used Southern blot analysis to demonstrate that TSG6 is a single-copy gene in the human and murine species. With the aid of a somatic cell hybrid mapping panel, TSG6 was assigned to human chromosome 2. Nuclear run-on analysis revealed that TNF produced a rapid, primary transcriptional activation of the TSG6 gene in normal human FS-4 fibroblasts. In order to learn more about the regulation of TSG6 gene expression, we cloned the TSG6 gene from a genomic library of human white blood cells. Sequencing of a 1.3-kilobase fragment of the 5'-flanking region of the TSG6 gene identified TATA-like and CAAT sequences near the transcription start site. In addition, potential binding sites for NF-IL-6, AP-1, interferon regulatory factors (IRF)-1 and -2, and glucocorticoid response elements were identified in the 5'-flanking region. A single transcription start site was identified by primer extension. Deletion analysis of the 5'-flanking region of the TSG6 DNA linked to the chloramphenicol acetyltransferase reporter gene revealed that a construct containing TSG6 DNA from positions -165 to +78 could be transcriptionally activated by interleukin(IL)-1, and to a lesser extent by TNF, upon transfection into FS-4 fibroblasts. The region that imparts inducibility by IL-1 or TNF (positions -165 to -58) contains potential binding sites for IRF-1 and -2, AP-1, and NF-IL-6. A region mediating transcriptional silencing was localized further upstream (between positions -332 and -165). The results suggest that TSG6 gene expression is regulated by an interplay of positively and negatively acting transactivating factors.

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