Chromatin ‘readers’ are central interpreters of the epigenome that facilitate cell-specific transcriptional programs and are therapeutic targets in cancer and inflammation. The Speckled Protein (SP) family of chromatin ‘readers’ in humans consists of SP100, SP110, SP140, and SP140L. SPs possess functional domains (SAND, PHD, bromodomain) that dock to DNA or post-translationally modified histones and a caspase activation and recruitment domain (CARD) to promote multimerization. Mutations within immune expressed SPs associate with numerous immunological diseases including Crohn’s disease, multiple sclerosis, chronic lymphocytic leukemia, veno-occlusive disease with immunodeficiency, as well as Mycobacterium tuberculosis infection, underscoring their importance in immune regulation. In this review, we posit that SPs are central chromatin regulators of gene silencing that establish immune cell identity and function.

染色质“阅读器”是表观基因组的核心解释器，可促进细胞特异性转录程序，并且是癌症和炎症的治疗靶点。人类染色质“阅读器”的斑点蛋白 (SP) 家族由 SP100、SP110、SP140 和 SP140L 组成。SP 拥有功能域（SAND、PHD、溴域），可与 DNA 或翻译后修饰的组蛋白对接，并具有半胱天冬酶激活和募集域 (CARD) 以促进多聚化。免疫表达的 SP 内的突变与许多免疫疾病有关，包括克罗恩病、多发性硬化症、慢性淋巴细胞白血病、具有免疫缺陷的静脉闭塞病以及结核分枝杆菌感染，强调了它们在免疫调节中的重要性。在这篇综述中，我们假设 SP 是基因沉默的中央染色质调节剂，可建立免疫细胞的身份和功能。