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Characterization of human Fas gene. Exon/intron organization and promoter region
1Department of Medicine, University of Alabama at Birmingham.
Abstract:
Ligation of the Fas cell-surface molecule induces apoptosis. Defective Fas-mediated apoptosis has been associated with spontaneous autoimmunity in mice. Using human Fas/Apo-1 cDNA as a probe, we have molecularly cloned and characterized the human Fas chromosomal gene. The gene consists of nine exons and spans more than 26 kilobases of DNA. The lengths of introns vary from > 14 kilobases at the 5' end of the gene to 152 base pairs upstream of the exon encoding the transmembrane domain. The domain structure of the human Fas is encoded by an exon or a set of exons. Primer extension analysis revealed three major transcription initiation sites. The promoter region lacked canonical "TATA" and "CAAT" boxes but was a "GC-rich" sequence, and contained consensus sequences for AP-1, GF-1, NY-Y, CP-2, EBP20, and c-myb. These data provide the first characterization of the human Fas gene and insight into its regulatory region.
Insights
Researchers characterized the human Fas gene, crucial for apoptosis and linked to autoimmunity. This study details its structure and regulatory elements, offering insights into its function.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Fas cell-surface molecule ligation triggers apoptosis.
- Defects in Fas-mediated apoptosis are linked to autoimmune diseases in mice.
Purpose of the Study:
- To molecularly clone and characterize the human Fas chromosomal gene.
- To investigate the regulatory elements of the human Fas gene.
Main Methods:
- Human Fas/Apo-1 cDNA was used as a probe for gene cloning.
- Gene structure, including exons and introns, was analyzed.
- Primer extension analysis identified transcription initiation sites.
- Promoter region analysis identified regulatory sequences.
Main Results:
- The human Fas gene was cloned and characterized, comprising nine exons and spanning over 26 kilobases.
- Intron lengths varied significantly, with the 5' end introns being over 14 kilobases.
- The promoter region is GC-rich, lacks TATA/CAAT boxes, and contains binding sites for transcription factors like AP-1 and c-myb.
- Three major transcription initiation sites were identified.
Conclusions:
- This study provides the first comprehensive characterization of the human Fas gene.
- The findings offer insights into the regulatory mechanisms controlling Fas gene expression.
- Understanding the human Fas gene structure and regulation is vital for studying apoptosis and autoimmunity.