mel‐18, a Polycomb group‐related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity.
The EMBO JournalPublished 1 November 1995Open access
Masamoto Kanno, M. Hasegawa, Akimasa Ishida, K Isono, M. Taniguchi
Citations129
SJR quartileQ1
SJR score4.82
SNIP1.93
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TL;DR
It is found that Mel‐18 acts as a transcriptional repressor via its target DNA sequence, 5′‐GACTNGACT‐3′, and this binding sequence is found within regulatory or non‐coding regions of various genes, suggesting diverse functions of mel‐18 as the mammalian homolog of the PcG gene.
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.
Keywords
Biochemistry, Genetics and Molecular Biology
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