Abstract：
During Drosophila development, Polycomb-group and Trithorax group proteins function to ensure correct maintenance of transcription patterns by epigenetically repressing or activating target gene expression. To get a deep insight into the PcG and trxG pathways, we investigated a BRCT domain-containing protein called PTIP, which was generally identified as a transcriptional coactivator and belongs to the TRR complex. At the genome scale, we sorted given PTIP-binding peaks into two groups: PTIP/TRR-cobound and PTIP/PC-cobound peaks. In particular, we found that PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Thus, we suggest that PTIP is a mediator rather than a dedicated co-activator along PcG and trxG pathways. Our hypothesis is further supported by the genetic assay: PTIP interacts genetically with either PcG or TrxG in a dosage-dependent manner, suggesting that PTIP functions as a co-factor of PcG/TrxG proteins. In addition, in accordance with the analysis of ChIP-seq, these genetic interactions correlate with modified ectopic HOX protein levels in imaginal discs, which reveals an essential role for PTIP in PcG-mediated Hox gene repression. Hence, we reveal a novel role for PTIP in the epigenetic regulation of gene expression along PcG and trxG pathways.
摘要：
在果蝇发育过程中,Polycomb组和Trithorax组蛋白通过表观遗传抑制或激活靶基因表达来确保正确维持转录模式。为了深入了解PcG和trxG途径，我们研究了一种名为PTIP的含有BRCT结构域的蛋白质，通常被鉴定为转录共激活因子，属于TRR复合物。在基因组规模上，我们将PTIP结合峰分为两组：PTIP/TRR共结合峰和PTIP/PC共结合峰。特别是,我们发现PTIP在TRR或PC占据区域介导H3K4me3/H3K27ac和H3K27me3组蛋白修饰之间的分子开关。因此，我们认为,PTIP是PcG和trxG通路的介质,而不是专用共激活剂.遗传分析进一步支持了我们的假设：PTIP以剂量依赖性方式与PcG或TrxG发生遗传相互作用，这表明PTIP作为PcG/TrxG蛋白的辅因子发挥作用。此外,根据ChIP-seq的分析，这些遗传相互作用与假象盘中改变的异位HOX蛋白水平相关，这揭示了PTIP在PcG介导的Hox基因抑制中的重要作用。因此，我们揭示了PTIP在沿PcG和trxG途径的基因表达的表观遗传调控中的新作用。
