Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing

• Published in: PLoS genetics 2020-08, Vol.16 (8), p.e1008962-e1008962
• Main Authors: Fresán, Ujué, Rodríguez-Sánchez, Maria A, Reina, Oscar, Corces, Victor G, Espinàs, M Lluisa
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Brain research; Cell cycle; Cell Cycle Proteins - genetics; Centromere - genetics; Chromatin; Chromatin - genetics; Chromosomal Proteins, Non-Histone - genetics; Chromosome Segregation - genetics; Chromosomes; Cohesin; Cohesins; Deoxyribonucleic acid; DNA; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Gene expression; Gene regulation; Gene Silencing; Genomes; Heterochromatin; Heterochromatin - genetics; Histone H3; Histones - genetics; Insects; Interphase; Interphase - genetics; Kinases; Mammals; Medicine and Health Sciences; Mitosis; Mitosis - genetics; Observations; Phosphorylation; Phosphotransferases; Physical Sciences; Physiological aspects; Polycomb group proteins; Polycomb-Group Proteins - genetics; Position-effect variegation; Protein Serine-Threonine Kinases - genetics; Proteins; Quantitative analysis; Research and Analysis Methods; Sister Chromatid Exchange - genetics; Threonine; Threonine - genetics; Variegation; Yeast
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008962

Haspin, a highly conserved kinase in eukaryotes, has been shown to be responsible for phosphorylation of histone H3 at threonine 3 (H3T3ph) during mitosis, in mammals and yeast. Here we report that haspin is the kinase that phosphorylates H3T3 in Drosophila melanogaster and it is involved in sister chromatid cohesion during mitosis. Our data reveal that haspin also phosphorylates H3T3 in interphase. H3T3ph localizes in broad silenced domains at heterochromatin and lamin-enriched euchromatic regions. Loss of haspin compromises insulator activity in enhancer-blocking assays and triggers a decrease in nuclear size that is accompanied by changes in nuclear envelope morphology. We show that haspin is a suppressor of position-effect variegation involved in heterochromatin organization. Our results also demonstrate that haspin is necessary for pairing-sensitive silencing and it is required for robust Polycomb-dependent homeotic gene silencing. Haspin associates with the cohesin complex in interphase, mediates Pds5 binding to chromatin and cooperates with Pds5-cohesin to modify Polycomb-dependent homeotic transformations. Therefore, this study uncovers an unanticipated role for haspin kinase in genome organization of interphase cells and demonstrates that haspin is required for homeotic gene regulation.