2011年4月21日
The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset
24 MARCH 2011 | VOL 471 | NATURE | 513-518
• SETDB1 significantly accelerated melanoma onset.
• Melanomas overexpressing SETDB1 were more aggressive and locally invasive than control.
• SETDB1 overexpression does not have the same effect as loss of p53 in tumour formation.
• SETDB1 overexpression led to a broad pattern of transcriptional changes.
• The direct targets of SETDB1 are the promoters of genes encoding developmental regulators,
including Hox genes.
• A major consequences of SETDB1 amplification is repression of SETDB1-bound target genes.
• The activity of the methyltransferase complex containing SETDB1 and SUV39H1 alters gene
expression in a way that leads to the acceleration of melanoma onset and to increased invasiveness.
• The majority of malignant human melanomas overexpress the SETDB1 protein.
• SETDB1 is focally amplified in a broad range malignancies, suggesting that alterations in histone
methyltransferase activity could define a biologically related subset of cancers.
（担当：Royhan）