Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin

Abstract

Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled is still unclear. Here, we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining global nucleosome organisation in fission yeast. We identified several key factors involved in heterochromatin silencing that interact genetically with Abo1: histone deacetylase Clr3, H3K9 methyltransferase Clr4, and HP1 homolog Swi6. Cells lacking Abo1 cultivated at 30 °C exhibit an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin has increased H3K9me2 but decreased H3K9me3 levels compared to wild-type. In contrast, facultative heterochromatin regions exhibit reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both the centromeres and subtelomeres, but not in a subset of heterochromatin islands in our condition. Thus, our work uncovers a role of Abo1 in stabilising directly or indirectly Clr4 recruitment to allow the H3K9me2 to H3K9me3 transition in heterochromatin.In eukaryotic cells, the regions of the chromatin that contain active genes are termed euchromatin, and these regions condense in mitosis to allow for chromosome segregation and decondense in interphase to allow for gene transcription 1 . The chromatin regions that remain condensed throughout the cell cycle are defined as heterochromatin regions and are transcriptionally repressed 2,3 . In general, heterochromatin can be defined molecularly by the modification of histone H3, specifically the absence of methylation on lysine 4 (H3K4me) and presence of methylation on lysine 9 (H3K9me) 4-6 . A conserved group of heterochromatin proteins, the heterochromatin protein 1 (HP1) family, specifically recognise heterochromatin regions by binding to H3K9me. Both di-and tri-methylation (H3K9me2/3) enable the binding of HP1 proteins to silence heterochromatin 7,8 . Heterochromatin regions can be further classified into constitutive and facultative heterochromatin 9,10 . Fission yeast, Schizosaccharomyces pombe, is an excellent model organism for chromatin studies because its heterochromatin organisation is similar to human cells 11,12 . Examples of constitutive heterochromatin regions in S. pombe are the pericentromeric regions that contain repetitive DNA sequences 13 . These regions are regulated by RNAi-dependent silencing machinery that involves protein Dcr1 and Ago1 14,15 . In contrast, the silencing of facultative heterochromatin, such as subtelomeric regions and heterochromatin islands, is mediated by RNAi-independent machinery that can be dynamically modulated to express genes required for the cell cycle or adaptation to the cell environment 16,17 . A subset of facultative heterochromatin islands, known as "determinant of selective removal" (DSR) islands, contain meiotic ...

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