Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing


Autoři: Ujué Fresán aff001;  Maria A. Rodríguez-Sánchez aff001;  Oscar Reina aff003;  Victor G. Corces aff004;  M. Lluisa Espinàs aff001
Působiště autorů: Institut de Biologia Molecular de Barcelona, IBMB-CSIC, Barcelona, Spain aff001;  Institute for Research in Biomedicine IRB, Barcelona, Spain aff002;  Bioinformatics and Biostatistics Unit, Institute for Research in Biomedicine IRB, Barcelona, Spain aff003;  Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America aff004
Vyšlo v časopise: Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing. PLoS Genet 16(8): e1008962. doi:10.1371/journal.pgen.1008962
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008962

Souhrn

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.

Klíčová slova:

Drosophila melanogaster – Heterochromatin – Chromatin – Insulators – Invertebrate genomics – Larvae – Mitosis – Salivary glands


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