ChIP-seq analysis done for MBD3 before and after SP140 knockout in Ramos cells

Sp140 is a lymphocytic-restricted protein, 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 cancer. 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 demonstrated that Sp140 interaction with PRC2 is functional and directs H3K27me3 deposition on a set of target genes related to cellular growth and leukaemia progression. We used ChIP-grade antibody for MBD3 and immunoprecipitated chromatin from wild type and SP140 KO Ramos cells