Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development

摘要

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 (also known as swsn-2.1) and its paralog encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether and 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 and 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 and 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 null mutants whereas is required for proper cell divisions. Using a proteomic approach, we identified -interacting proteins needed for early cell divisions, such as and , and also nuclear envelope proteins such as . mutants phenocopy loss-of-function, and we observed that href="http://www.wormbase.org/db/get?name=WBGene00015971;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=4788132&issue-id=266538&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">SWSN-2.2 and href="http://www.wormbase.org/db/get?name=WBGene00003210;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=4788132&issue-id=266538&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that href="http://www.wormbase.org/db/get?name=WBGene00015971;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=4788132&issue-id=266538&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of href="http://www.wormbase.org/db/get?name=WBGene00003210;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=4788132&issue-id=266538&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">MEL-28 to the nuclear periphery.