Disease relevance of SETD8

• In the 51 breast cancer tissue samples tested, the SET8 CC genotype was associated with reduced SET8, but not miR-502, transcript levels [1].

High impact information on SETD8

• Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine [2].
• Finally, analysis of the product specificity indicates that hSET8 is a monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division [2].
• Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes [3].
• These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted [3].
• Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation were inversely correlated to transient H4 Lys 16 acetylation in early S-phase [3].

Biological context of SETD8

• We demonstrate that the Drosophila SET8 homolog has the same substrate specificity as its human counterpart [4].
• Indeed, upregulation of PR-Set7 expression upon loss of HCF-1 leads to improper mitotic H4-K20 methylation and cytokinesis defects [5].

Associations of SETD8 with chemical compounds

• We have purified a human histone H4 lysine 20 methyltransferase and cloned the encoding gene, PR/SET07 [6].

References