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PMID:10918580

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Citation

Finzer, P, Soto, U, Delius, H, Patzelt, A, Coy, JF, Poustka, A, zur Hausen, H and Rösl, F (2000) Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role of the chromatin structure and AP-1 composition. Oncogene 19:3235-44

Abstract

The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts. In contrast, MCP-1 transcription is absent in tumorigenic segregants derived from the same hybrids or in parental HeLa cells. Selectivity of MCP-1 transcription, which is regulated at the level of initiation of transcription, is mainly based on differences in the location and extension of DNAse I-hypersensitive regions (DHSR) at both ends of the gene. While TNF-alpha only moderately increases the sensitivity of pre-existing 5'-DHSRs, a 3'-end DHSR became strongly induced exclusively in non-malignant hybrids. DNA sequencing showed that the 3'-DHSR coincides with an additional AP-1 site located approximately 600 bp downstream of the polyadenylation site. Analyses of AP-1 composition revealed that MCP-1 is only expressed in those cells where jun-family members were mainly heterodimerized with the fos-related protein fra-1. In contrast, in tumorigenic cells the 1: 1 ratio between jun and fra-1 is disturbed and the MCP-1 gene is no longer expressed. Hence, alterations in the heterodimerization pattern of AP-1 and its selective accessibility to opened chromatin may represent a novel regulatory pathway in the regulation of chemokines in malignant and non-malignant HPV-positive cells.

Links

PubMed Online version:10.1038/sj.onc.1203643

Keywords

Base Sequence; Cell Line; Cell Nucleus/metabolism; Chemokine CCL2/genetics; Chromatin/physiology; Chromosome Mapping; Deoxyribonuclease I/metabolism; Gene Expression Regulation/drug effects; HeLa Cells; Humans; Molecular Sequence Data; Papillomaviridae/genetics; RNA, Messenger; Sequence Analysis, DNA; Transcription Factor AP-1/genetics; Transcription Factor AP-1/metabolism; Transcription, Genetic/drug effects; Tumor Necrosis Factor-alpha/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FOS

involved_in

GO:0006366: transcription by RNA polymerase II

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOS

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:JUN

located_in

GO:0000228: nuclear chromosome

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FOSL1

located_in

GO:0005634: nucleus

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FOSL1

involved_in

GO:0006935: chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOSL1

part_of

GO:0005634: nucleus

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FOSL1

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FOSL1

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOSL1

involved_in

GO:0006968: cellular defense response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:JUN

part_of

GO:0000228: nuclear chromosome

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete


See also

References

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