Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [ATAC-Seq]. Homo sapiens

Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown. Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients. Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity. Overall design: ATAC-seq in human macrophages stimulated with IFNg for 24h, and LPS stimulation for 4 hours: siRNA mediated knockdown of SP140 versus controls.