Seminar - Ke Zhang Reid

Dr. Ke Zhang Reid is pictured
April 10, 2023 - 12:00pm
Location: 
601 Fairchild
Associate Professor
Department of Biology
 
Host: Songtao Jia
 
Title: Epigenetic regulation by Histone H3 Methyltransferases and Demethylases in Schizosaccharomyces pombe

Abstract: The organization of eukaryotic chromatin into silenced heterochromatin and active euchromatin regions plays a critical role in regulating gene expression by controlling the accessibility of DNA. In Schizosaccharomyces pombe, Set1 is the primary H3 lysine (K) 4 methyltransferase, enriched at the promoters of actively transcribed genes. In contrast, Clr4/SUV39h methyltransferase targets H3K9 and is a hallmark of heterochromation. The H3K4/H3K9 demethylases, Lsd1 and Lsd2, are highly conserved, but their functional crosstalk with methyltransferases remains poorly understood. Our recent results suggest that Lsd1 and Lsd2 function to repress heterochromatic transcripts at heterochromatic regions, partially through a mechanism independent of amine oxidase-related demethylation activities. In addition, without the amine-oxidase activities of Lsd proteins, cells are defective in the RNAi-independent maintenance and re-establishment of heterochromatin at the mating-type locus. Lsd1 and Lsd2 interact with subunits of Clr4- or Set1-associated complexes. Clr4 and Set1 modulate the protein levels of Lsd1 and Lsd2 in opposite ways through a ubiquitin-proteasome-dependent pathway. In the absence of Set1, Lsd1/2 protein levels are reduced, while in the absence of Clr4, Lsd1/2 protein levels are enhanced. During heat stress, the levels of Lsd1/2 are upregulated in a Set1-dependent manner, and these increased protein levels are crucial for differential gene expression during heat stress. Overall, the results suggest a cross-regulatory in which Set1 and Clr4 methyltransferases control the protein levels of Lsd1/2 demethylases to shape the dynamic histone modification landscape.

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