The epigenetic role of Hamlet in neurogenesis

哈姆雷特是进化上保守的果蝇Prdm转录因子家族成员，已经证明哈姆雷特控制着黑腹果蝇外部感觉器官谱系中的非神经细胞与神经细胞的命运（Moore等）。科学。2002。297:1355-8)。通过染色质免疫沉淀和蛋白质组学方法，我阐明了哈姆雷特改变Notch靶基因位点的组蛋白密度和组蛋白甲基化。《哈姆雷特》包含两个锌指簇；PR （PRDI-BF1和RIZ同源）结构域，是SET结构域的衍生物；c端结合蛋白（CtBP）转录共抑制因子结合位点。所有这些结构域在秀丽隐杆线虫（Egl43）到小鼠和人（Prdm16）的HAM同源物中高度保守。通过使用缺乏这些保守的哈姆雷特结构域的转基因果蝇，我们确定锌指簇和CtBP结构域都是哈姆雷特功能所需的。

Hamlet is the evolutionarily conserved Drosophila Prdm transcription factor family member and it has been demonstrated that Hamlet controls non-neural versus neural cell fate in the Drosophila melanogaster External Sensory Organ lineage (Moore et al. Science. 2002 297:1355-8). By means of chromatin immunoprecipitation and proteomic approaches, I elucidated that Hamlet modifies histone density and histone methylation at Notch target gene loci. Hamlet contains two zinc finger clusters; a PR (PRDI-BF1 and RIZ homology) domain, a derivative of the SET domain; and a C-terminal Binding Protein (CtBP) transcriptional co-repressor binding site. All these domains are highly conserved in HAM homologues from C. elegans (Egl43) to mouse and humans (Prdm16). By using transgenic flies which lack these conserved Hamlet domains, we determined that both zinc finger clusters and CtBP domains are required for proper Hamlet function.