Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing

• Type of Material: Article
• Authors: Ujué Fresan, Institut de Biologia Molecular de Barcelona; Maria A. Rodriguez-Sanchez, Institut de Biologia Molecular de Barcelona; Oscar Reina, Institute for Research in Biomedicine IRB; Victor Corces, Emory University; M. Lluisa Espinas, Institut de Biologia Molecular de Barcelona
• Language: English
• Date: 2020-08-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Fresán et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pgen.1008962
• Title of Journal or Parent Work: PLOS GENETICS
• Volume: 16
• Issue: 8
• Start Page: e1008962
• End Page: e1008962
• Grant/Funding Information: This work was supported by the Spanish Ministerio de Economia y Competitividad (BFU2013-48712-P) and the Generalitat de Catalunya (SGR2017-475). U. F. and M. R-S. acknowledge receipt of doctoral fellowships from Consejo Superior de Investigaciones Cientificas and Ministerio de Economia y Competitividad respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: CENTROMERE; TRANSCRIPTION; THR-3 PHOSPHORYLATION; Genetics & Heredity; PROTEINS; SISTER-CHROMATID COHESION; DROSOPHILA; Science & Technology; ELEMENTS; ORGANIZATION; Life Sciences & Biomedicine; DOMAINS; BITHORAX COMPLEX
• Research Categories: Biology, Cell; Biology, Genetics

Abstract

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.