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mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive
M Kanno1, M Hasegawa, A Ishida
1Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
Abstract:
The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a secondary structure, including a RING-finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel-18/Bmi-1 might be expected to have similar activities. Here we have analyzed the function of mel-18 and found that Mel-18 acts as a transcriptional repressor via its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is found within regulatory or non-coding regions of various genes, including the c-myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene.
Insights
The mel-18 gene acts as a transcriptional repressor, regulating key genes like c-myc and Hox. Unlike its proto-oncogene relative bmi-1, mel-18 exhibits tumor suppressor activity.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Mammalian mel-18 and bmi-1 share structural similarities with Drosophila Polycomb group (PcG) proteins.
- Drosophila PcG proteins are known transcriptional repressors involved in chromatin modification.
Purpose of the Study:
- To investigate the functional role of the mammalian mel-18 gene.
- To determine mel-18's mechanism of transcriptional regulation and its potential in cancer.
Main Methods:
- Analysis of mel-18 gene function.
- Identification of mel-18's DNA binding sequence.
- Comparison of mel-18 and bmi-1 activities.
Main Results:
- Mel-18 functions as a transcriptional repressor, binding to the sequence 5'-GACTNGACT-3'.
- This binding site is present in regulatory regions of important genes, including c-myc, bcl-2, and Hox.
- Mel-18 demonstrates tumor suppressor activity, contrasting with bmi-1's proto-oncogenic role.
Conclusions:
- Mel-18 is a mammalian PcG homolog with diverse regulatory functions.
- Mel-18 acts as a transcriptional repressor and possesses tumor suppressor properties.