An essential role for PTIP in mediating Hox gene regulation along PcG and trxG pathways

• Published in: The FEBS journal 2022-10, Vol.289 (20), p.6324-6341
• Main Authors: Cheng, Qian, Xie, Hao, Zhang, Xiao‐Yan, Wang, Ming‐Ying, Bi, Cai‐Li, Wang, Qiang, Wang, Rui, Fang, Ming
• Format: Article
• Language: English
• Subjects: Drosophila; Epigenetics; Gene expression; Gene regulation; Genetic analysis; Genomes; histone modification; Histones; HOX; HOX gene; HOX protein; Imaginal discs; Kinases; Molecular machines; PcG/trxG; Polycomb group proteins; Proteins; PTIP
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.16541

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. In this study, we found that PTIP colocalizes with either TrxG or PcG. In particular, PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Furthermore, ptip genetically enhances PcG and suppresses trxG in Drosophila development. Hence, we reveal a novel role of PTIP, which is working as a mediator along PcG and trxG pathways.