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Published on: September 26, 2013
The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein
1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Abstract:
The ces-1 and ces-2 genes of C. elegans control the programmed deaths of specific neurons. Genetic evidence suggests that ces-2 functions to kill these neurons by negatively regulating the protective activity of ces-1, ces-2 encodes a protein closely related to the vertebrate PAR family of bZIP transcription factors, and a ces-2/ces-1-like pathway may play a role in regulating programmed cell death in mammalian lymphocytes. Here we show that ces-1 encodes a Snail family zinc finger protein, most similar in sequence to the Drosophila neuronal differentiation protein Scratch. We define an element important for ces-1 regulation and provide evidence that CES-2 can bind to a site within this element and thus may directly repress ces-1 transcription. Our results suggest that a transcriptional cascade controls the deaths of specific cells in C. elegans.
Insights
The ces-1 and ces-2 genes in C. elegans regulate programmed cell death. CES-2 directly represses ces-1 transcription, revealing a transcriptional cascade controlling cell death.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- The ces-1 and ces-2 genes govern programmed cell death of specific neurons in C. elegans.
- ces-2 negatively regulates ces-1's protective function, indicating a role in neuronal apoptosis.
- A ces-2/ces-1 pathway may be conserved in mammalian lymphocyte programmed cell death.
Purpose of the Study:
- To elucidate the molecular mechanism by which ces-2 regulates ces-1.
- To characterize the protein encoded by ces-1.
- To investigate the potential direct interaction between CES-2 and ces-1 regulatory elements.
Main Methods:
- Gene cloning and sequence analysis to identify the ces-1 gene product.
- Bioinformatic analysis to determine protein family relationships.
- Reporter assays and DNA-binding experiments to assess CES-2's regulatory function on ces-1.
Main Results:
- ces-1 encodes a Snail family zinc finger protein, homologous to Drosophila Scratch.
- A regulatory element crucial for ces-1 expression was identified.
- CES-2 demonstrated binding to this element, suggesting direct transcriptional repression of ces-1.
Conclusions:
- The ces-1 gene product is a Snail family transcription factor.
- CES-2 directly represses ces-1 transcription, likely via binding to a specific regulatory element.
- These findings support a model where a transcriptional cascade controls programmed cell death in C. elegans.
