The Cross-Regulation Between Set1, Clr4, and Lsd1/2 in < i > Schizosaccharomyces pombe < /i >

by Haoran Liu, Bahjat Fadi Marayati, David de la Cerda, Brendan Matthew Lemezis, Jieyu Gao, Qianqian Song, Minghan Chen, Ke Zhang Reid

Eukaryotic chromatin is organized into either silenced heterochromatin or relaxed euchromatin regions, which controls the accessibility of transcriptional machinery and thus regulates gene expression. In fission yeast,Schizosaccharomyces pombe, Set1 is the sole H3K4 methyltransferase and is mainly enriched at the promoters of actively transcribed genes. In contrast, Clr4 methyltransferase initiates H3K9 methylation, which has long been regarded as a hallmark of heterochromatic silencing. Lsd1 and Lsd2 are two highly conserved H3K4 and H3K9 demethylases. As these histone-modifying enzymes perform critical roles in maintaining histone methylation patterns and, consequently, gene expression profiles, cross-regulations among these enzymes are part of the complex regulatory networks. Thus, elucidating the mechanisms that govern their signaling and mutual regulations remains crucial. Here, we demonstrated that C-terminal truncation mutants,lsd1- ΔHMG andlsd2- ΔC, do not compromise the integrity of the Lsd1/2 complex but impair their chromatin-binding capacity at the promoter region of target genomic loci. We identified protein-protein interactions between Lsd1/2 and Raf2 or Swd2, which are the subunits of the Clr4 complex (CLRC) and Set1-associated complex (COMPASS), respectively. We showed that Clr4 and Set1 modulate the protein levels of Lsd1 a...

Source: PLoS Genetics - January 5, 2024 Category: Genetics & Stem Cells Authors: Haoran Liu Source Type: research