Tamburri Simone, Zucchelli Chiara, Matafora Vittoria, Zapparoli Ettore, Jevtic Zivojin, Farris Francesco, Iannelli Fabio, Musco Giovanna, Bachi Angela
IFOM ETS, The AIRC Institute of Molecular Oncology, Via Adamello 16, 16039 Milano, Italy.
Biomolecular NMR Laboratory, Division of Genetics and Cell biology, IRCCS Ospedale San Raffaele, Via Olgettina 58, 20132 Milano, Italy.
Nucleic Acids Res. 2025 Feb 8;53(4). doi: 10.1093/nar/gkae1215.
SP140, a lymphocytic-restricted protein, is an epigenetic reader working as a corepressor of genes implicated in inflammation and orchestrating macrophage transcriptional programs to maintain cellular identity. 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.
SP140是一种淋巴细胞限制性蛋白，是一种表观遗传阅读器，作为炎症相关基因的共抑制因子，协调巨噬细胞转录程序以维持细胞特性。SP140表达降低与自身免疫性疾病和血癌均有关联。然而，将SP140蛋白水平改变与对免疫反应和细胞生长的有害影响联系起来的分子机制，以及SP140促进基因沉默所通过的相互作用分子，仍然不清楚。在这项研究中，我们在两种伯基特淋巴瘤细胞系中应用了多组学方法（即相互作用组学、染色质免疫沉淀测序和蛋白质组学），以鉴定内源性SP140的相互作用分子和靶基因。我们发现SP140与PRC2和NuRD复合物相互作用，并且我们表明这些相互作用具有功能，因为SP140指导H3K27me3在一组与细胞生长和白血病进展相关的靶基因上的沉积以及NuRD的结合。
