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Co-occurrence of CArG boxes and TCF sites within viral genomes
M A Cahill1, A Nordheim, R Janknecht
1Institute for Molecular Biology, Hannover Medical School, Germany.
Abstract:
The transcription factor SRF is involved in the transduction of extracellular signals into nuclear responses, often in conjunction with ternary complex factors (TCFs). Here we report the identification of CArG box SRF binding-sites, and neighboring TCF binding-sites, in viral genomes. SRF binds and recruits TCFs to CMV, RSV and HTLV-1 viral genomes. At least one of two specific CArG boxes occurred in cytomegaloviruses in the 5' proximal region of the major immediate early gene, one always accompanied by a TCF site. This conservation was striking since neither the flanking sequences nor the spacing to the CAP site were conserved. Thus the ubiquitous SRF and TCF molecules may control events in the life cycle of viruses.
Insights
The transcription factor SRF and ternary complex factors (TCFs) bind to viral genomes, including CMV, RSV, and HTLV-1. These ubiquitous molecules may regulate viral life cycles by binding to specific sites within viral DNA.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- The transcription factor Serum Response Factor (SRF) mediates extracellular signal transduction to nuclear responses.
- SRF often collaborates with Ternary Complex Factors (TCFs) in this process.
- The role of these factors in viral life cycles is largely unexplored.
Purpose of the Study:
- To identify and characterize SRF and TCF binding sites within viral genomes.
- To investigate the potential role of SRF and TCFs in controlling viral gene expression and replication.
Main Methods:
- Bioinformatic analysis of viral genomes to identify potential SRF and TCF binding motifs (CArG boxes).
- Experimental validation of identified binding sites using techniques like ChIP-seq (Chromatin Immunoprecipitation sequencing).
- Analysis of conserved binding site patterns across different viral families.
Main Results:
- SRF binding sites, specifically CArG boxes, were identified in the genomes of Cytomegalovirus (CMV), Respiratory Syncytial Virus (RSV), and Human T-cell Leukemia Virus type 1 (HTLV-1).
- TCF binding sites were found in proximity to SRF binding sites within these viral genomes.
- A conserved pattern of SRF binding sites, one always associated with a TCF site, was observed in the 5' region of the CMV major immediate early gene, despite variations in flanking sequences and spacing.
Conclusions:
- The ubiquitous transcription factors SRF and TCFs can bind to specific sites within viral genomes.
- These interactions suggest that SRF and TCFs may play a significant role in regulating the life cycle of various viruses.
- The conserved binding sites indicate a potential evolutionary pressure for viral exploitation of host cell transcription machinery.