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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3T3 Cells
-
Animals
-
Base Sequence
-
Binding Sites
-
DNA / metabolism
-
DNA, Single-Stranded / metabolism
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / metabolism
-
Drosophila Proteins*
-
Gene Expression Regulation*
-
Genes, Tumor Suppressor*
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Molecular Sequence Data
-
Neoplasms, Experimental / genetics
-
Nuclear Proteins / genetics
-
Oligodeoxyribonucleotides
-
Oligonucleotides, Antisense / metabolism
-
Polycomb Repressive Complex 1
-
Proteins / genetics*
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins / genetics
-
Random Amplified Polymorphic DNA Technique
-
Repressor Proteins*
-
Sequence Homology, Nucleic Acid
-
Transcription, Genetic
-
Transfection
Substances
-
Bmi1 protein, mouse
-
DNA, Single-Stranded
-
DNA-Binding Proteins
-
Drosophila Proteins
-
MAS1 protein, human
-
Nuclear Proteins
-
Oligodeoxyribonucleotides
-
Oligonucleotides, Antisense
-
PCGF2 protein, human
-
Pc protein, Drosophila
-
Pcgf6 protein, mouse
-
Proteins
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins
-
Repressor Proteins
-
DNA
-
Polycomb Repressive Complex 1