Journey with Dr. Levy into the heart of cellular fate determination and the role of the polycomb repressive complex 2 (PRC2) in it. Histone 3 lysine 27 methylation (H3K27me3) marks, crucial for cellular bifurcation during development, have remained a mystery—until now. Dr. Levy introduces the cutting-edge EBdCas9 technology, a fusion of a computationally designed protein and the infamous dCas9, to shed light on this enigmatic process. When targeted at specific genes, this tool reveals precise locations where H3K27me3 and EZH2 operate, leading to fascinating insights such as the discovery of a functional distal TATA box upstream of the TBX18 transcription start site.

Dive deeper to understand the power of EBdCas9, from revealing the most significant H3K27me3 marks in promoter regions to controlling transcriptional activation organically. Dr. Levy’s work also paints a larger picture about the nature of H3K27me3 marks on promoter regions, challenging our previous understanding and suggesting that many broad marks might be indiscriminate. With an eye to the future, this episode discusses the potential of EBdCas9 not only as an invaluable research tool but also as a revolutionary method to treat diseases like cancer. This isn't just about decoding genes; it's about rewiring our understanding of epigenomic memory, and how we might shape it for the future of medicine.

Keyword List:

• Epigenomic Regulation
• PRC2
• Histone 3 lysine 27 methylation (H3K27me3)
• EBdCas9 Technology
• dCas9
• TATA Box
• TBX18
• Gene Activation
• Transcriptional Activation
• TBP Recruitment
• Epigenomic Memory
• Cellular Fate Determination
• Cancer Treatment Potential

doi: 10.1016/j.celrep.2022.110457. PMID: 35235780.