title: Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development.
abstract: SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether ham-3 and swsn-2.2 have different functions during C. elegans development since they encode proteins that are probably mutually exclusive in a given SWI/SNF complex. We found that ham-3 and swsn-2.2 display similar functions in vulva specification, germline development, and intestinal cell proliferation, but have distinct roles in embryonic development. Accordingly, we detected functional redundancy in some developmental processes and demonstrated by RNA sequencing of RNAi-treated L4 animals that ham-3 and swsn-2.2 regulate the expression of a common subset of genes but also have specific targets. Cell lineage analyses in the embryo revealed hyper-proliferation of intestinal cells in ham-3 null mutants whereas swsn-2.2 is required for proper cell divisions. Using a proteomic approach, we identified SWSN-2.2-interacting proteins needed for early cell divisions, such as SAO-1 and ATX-2, and also nuclear envelope proteins such as MEL-28. swsn-2.2 mutants phenocopy mel-28 loss-of-function, and we observed that SWSN-2.2 and MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of MEL-28 to the nuclear periphery.
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Ertl
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain C. elegans Core Facility, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Porta-de-la-Riva
authors.affiliation: Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gómez-Orte
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Karinna
authors.initials: K
authors.lastname: Rubio-Peña
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Aristizábal-Corrales
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eric
authors.initials: E
authors.lastname: Cornes
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontrodona
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Osteikoetxea
authors.affiliation: Andalusian Center for Developmental Biology (CABD), Consejo Superior de Investigaciones Científicas/Junta de Andalucia/Universidad Pablo de Olavide, 41013 Seville, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Andalusian Center for Developmental Biology (CABD), Consejo Superior de Investigaciones Científicas/Junta de Andalucia/Universidad Pablo de Olavide, 41013 Seville, Spain.
authors.forename: Peter
authors.initials: P
authors.lastname: Askjaer
authors.affiliation: Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cabello
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain jceron@idibell.cat.
authors.forename: Julián
authors.initials: J
authors.lastname: Cerón
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins; D047108:Embryonic Development / Q000235:genetics; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C574024:SAO-1 protein, C elegans; C514979:mel-28 protein, C elegans
keywords: Caenorhabditis elegans; SWI/SNF; chromatin; development; nuclear envelope