A team of scientists led by Prof. ZHAO Yun at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, have identified a novel and positive role for polycomb repressive complex in transcriptional regulation. 

The highly conserved Polycomb group (PcG) proteins maintain heritable transcription repression of the genes essential for development from fly to mammals. However, several isolated studies in Drosophila and mammals suggest a positive regulatory role of PcGs in transcription, but the underlying mechanism is largely unknown. Most of these studies have focused on the positive role of PcGs during carcinogenesis, whereas such regulation during normal development has been poorly investigated. It is therefore important to clarify the role of the PcG proteins in promoting transcription during normal developmental process, and if so, to understand the mechanism by which the PcG proteins do that. 

Supervised by Prof. ZHAO Yun, LV Xiangdong and colleagues reported a Pc-mediated, H3K27me3-dependent positive transcriptional regulation of Senseless (Sens), a key transcription factor required for development. Pc regulates Sens expression by targeting H4K20me1 at the Sens locus. Further bioinformatics analysis at genome-wide level indicates that the existence of H4K20me1 acts as a selective mark for positive transcriptional regulation by Pc/H3K27me3. Both the intensities and specific patterns of Pc and H3K27me3 are important for the fates of target gene transcription.

Moreover, binding of transcription factor Broad (Br), which physically interacts with Pc and positively regulates the transcription of Sens, is observed in Pc⁺H3K27me3⁺H4K20me1⁺ genes, but not in Pc⁺H3K27me3⁺H4K20me1⁻ genes. In all, this study reveals that, coupling the transcription factor Br, Pc positively regulates transcription of Pc⁺H3K27me3⁺H4K20me1⁺ genes in developing Drosophila wing disc. 

This study entitled “A positive role for polycomb in transcriptional regulation via H4K20me1” was published online by Cell Research on 22 March, 2016. 

This work was supported by grants from the National Natural Science Foundation of China, Strategic Priority Research Program of the Chinese Academy of Sciences, and the Chinese Academy of Sciences. 

Pc positively regulates transcription of Pc⁺H3K27me3⁺H4K20me1⁺ genes in developing Drosophila wing disc. (Image by ZHAO Yun’s group & WEI Gang’s group)