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Reduced SP140 expression is associated both to autoimmune diseases and blood cancers. However, the molecular mechanisms that link SP140 altered protein levels to detrimental effects on the immune response and cellular growth, as well as the interactors through which SP140 promotes gene silencing, remain elusive. In this work, we have applied a multi-omics approach (i.e. interactomics, ChIP-seq and proteomics) in two Burkitt lymphoma cell lines to identify both interactors and target genes of endogenous SP140. We found that SP140 interacts with the PRC2 and NuRD complexes, and we showed that these interactions are functional as SP140 directs H3K27me3 deposition and NuRD binding on a set of target genes implicated in cellular growth and leukemia progression.<\/jats:p>","DOI":"10.1093\/nar\/gkae1215","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T18:28:59Z","timestamp":1735064939000},"source":"Crossref","is-referenced-by-count":3,"title":["SP140 represses specific loci by recruiting polycomb repressive complex 2 and NuRD complex"],"prefix":"10.1093","volume":"53","author":[{"given":"Simone","family":"Tamburri","sequence":"first","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zucchelli","sequence":"additional","affiliation":[{"name":"Biomolecular NMR Laboratory, Division of Genetics and Cell biology, IRCCS Ospedale San Raffaele , Via Olgettina 58 , 20132\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Matafora","sequence":"additional","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-7902","authenticated-orcid":false,"given":"Ettore","family":"Zapparoli","sequence":"additional","affiliation":[{"name":"Center for Omics Sciences, IRCCS Ospedale San Raffaele , Via Olgettina 58 , 20132\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zivojin","family":"Jevtic","sequence":"additional","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Farris","sequence":"additional","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2777-1417","authenticated-orcid":false,"given":"Fabio","family":"Iannelli","sequence":"additional","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0469-2994","authenticated-orcid":false,"given":"Giovanna","family":"Musco","sequence":"additional","affiliation":[{"name":"Biomolecular NMR Laboratory, Division of Genetics and Cell biology, IRCCS Ospedale San Raffaele , Via Olgettina 58 , 20132\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4842-6556","authenticated-orcid":false,"given":"Angela","family":"Bachi","sequence":"additional","affiliation":[{"name":"IFOM ETS, The AIRC Institute of Molecular Oncology , Via Adamello 16 , 16039\u00a0 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"2025030421244713200_B1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.it.2020.04.007","article-title":"The speckled protein (SP) family: immunity's chromatin readers","volume":"41","author":"Fraschilla","year":"2020","journal-title":"Trends Immunol."},{"key":"2025030421244713200_B2","doi-asserted-by":"crossref","first-page":"29198","DOI":"10.1074\/jbc.271.46.29198","article-title":"Identification and characterization of a leukocyte-specific component of the nuclear body","volume":"271","author":"Bloch","year":"1996","journal-title":"J. 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