Start Date
2023
Description
Enhancers of Zeste homolog proteins (EZH1 and EZH2) play a critical role in regulating gene transcription during development. The typical function of EZH2 and its homolog EZH1 is catalyzing the trimethylation of histone three at lysine 27 (H3K27) to repress gene expression through the PRC2 complex. In cancer, EZH2 is often over-expressed or mutated, leading to the silencing of tumor suppressor genes and a worse prognosis of the disease. Research on EZH1 and EZH2 in cancer has focused on their canonical function and has culminated in therapies that target their enzymatic activity. However, studies have found that drugs that inhibit EZH2's canonical function have mild effects in decreasing growth in specific cancers. Enzymatic inhibitor therapies may be ineffective in some cancers because they are unable to inhibit EZH1 and EZH2’s non-canonical function in increasing gene expression. A study found that in leukemia cells, EZH2 shows pronounced colocalization with acetylated histone three at lysine 9 and lysine 27, markers of transcriptional activation. EZH2 was also found to associate with the transcription factors cMyc and p300 and upregulate their target genes, increasing cancer cell proliferation. The EZH2-TAD was demonstrated to be crucial for recruiting cMyc and p300 and for upregulating oncogenes. Interestingly, the transcriptional activator p300 was also found to be crucial for EZH2-driven gene upregulation. , Therefore, we investigated the role of the TAD and p300 in the noncanonical function of EZH1 and EZH2. Here, we show that EZH1 interacts with p300 and activates its histone acetyltransferase catalytic activity through its TAD. We propose that EZH1 can activate gene expression through recruiting and modulating p300 HAT activity
Recommended Citation
Tsurh, Visakuo; Xu, Longxia; and Shi, Xiaobing, "Understanding the non-Canonical function of EZH1/2 in Gene Activation" (2023). Summer Research. 46.
https://digitalcommons.calvin.edu/summer_research/2023/Posters/46
Included in
Understanding the non-Canonical function of EZH1/2 in Gene Activation
Enhancers of Zeste homolog proteins (EZH1 and EZH2) play a critical role in regulating gene transcription during development. The typical function of EZH2 and its homolog EZH1 is catalyzing the trimethylation of histone three at lysine 27 (H3K27) to repress gene expression through the PRC2 complex. In cancer, EZH2 is often over-expressed or mutated, leading to the silencing of tumor suppressor genes and a worse prognosis of the disease. Research on EZH1 and EZH2 in cancer has focused on their canonical function and has culminated in therapies that target their enzymatic activity. However, studies have found that drugs that inhibit EZH2's canonical function have mild effects in decreasing growth in specific cancers. Enzymatic inhibitor therapies may be ineffective in some cancers because they are unable to inhibit EZH1 and EZH2’s non-canonical function in increasing gene expression. A study found that in leukemia cells, EZH2 shows pronounced colocalization with acetylated histone three at lysine 9 and lysine 27, markers of transcriptional activation. EZH2 was also found to associate with the transcription factors cMyc and p300 and upregulate their target genes, increasing cancer cell proliferation. The EZH2-TAD was demonstrated to be crucial for recruiting cMyc and p300 and for upregulating oncogenes. Interestingly, the transcriptional activator p300 was also found to be crucial for EZH2-driven gene upregulation. , Therefore, we investigated the role of the TAD and p300 in the noncanonical function of EZH1 and EZH2. Here, we show that EZH1 interacts with p300 and activates its histone acetyltransferase catalytic activity through its TAD. We propose that EZH1 can activate gene expression through recruiting and modulating p300 HAT activity