SP140 Represses Specific Loci by Recruiting Polycomb Repressive Complex 2 and NuRD Complex

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2024 Dec 24

PMID 39718989

Authors

Simone Tamburri

Chiara Zucchelli

Vittoria Matafora

Ettore Zapparoli

Zivojin Jevtic

Francesco Farris

Fabio Iannelli

Giovanna Musco

Angela Bachi

Affiliations

Soon will be listed here.

Abstract

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.

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