Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation.
Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation.
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DOI：
10.1038/s41590-021-00928-y
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发表时间：
2021-06
影响因子：
30.5
通讯作者：
Kuo AJ
中科院分区：
文献类型：
--
作者：
Cheung P;Schaffert S;Chang SE;Dvorak M;Donato M;Macaubas C;Foecke MH;Li TM;Zhang L;Coan JP;Schulert GS;Grom AA;Henderson LA;Nigrovic PA;Elias JE;Gozani O;Mellins ED;Khatri P;Utz PJ;Kuo AJ
染色质在免疫细胞分化期间经历广泛的重编程。在这里，我们报告了在单核细胞向巨噬细胞发育过程中，受控制的组蛋白H3氨基末端蛋白水解裂解（H3ΔN）的抑制。人外周血单核细胞中的这种丰富的组蛋白标记物由中性粒细胞丝氨酸蛋白酶（NSP）组织蛋白酶G、中性粒细胞弹性蛋白酶和蛋白酶3催化。随着单核细胞成熟为巨噬细胞，NSP被抑制。综合表观基因组分析揭示了单核细胞系和原代单核细胞中基因组中广泛的H3ΔN分布，这在完全分化的巨噬细胞中基本上检测不到。H3ΔN在允许的染色质和活跃转录的基因处富集。单核细胞中的同时NSP耗尽导致H3ΔN损失并进一步增加染色质可接近性，这可能为基因表达重编程准备染色质。重要的是，H3ΔN在来自全身性幼年特发性关节炎（sJIA）患者的单核细胞中减少，sJIA是一种具有显著巨噬细胞参与的自身炎症性疾病。总之，我们发现了一个表观遗传机制，启动染色质，以促进巨噬细胞的发展。
Chromatin undergoes extensive reprogramming during immune cell differentiation. Here we report repression of controlled histone H3 amino-terminus proteolytic cleavage (H3ΔN) during monocyte-to-macrophage development. This abundant histone mark in human peripheral blood monocytes is catalyzed by neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase, and proteinase 3. NSPs are repressed as monocytes mature into macrophages. Integrative epigenomic analysis reveals widespread H3ΔN distribution across the genome in a monocytic cell line and primary monocytes, which becomes largely undetectable in fully differentiated macrophages. H3ΔN is enriched at permissive chromatin and actively transcribed genes. Simultaneous NSP depletion in monocytic cells results in H3ΔN loss and further increase in chromatin accessibility, which likely primes the chromatin for gene expression reprogramming. Importantly, H3ΔN is reduced in monocytes from patients with systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease with prominent macrophage involvement. Together, we uncover an epigenetic mechanism that primes the chromatin to facilitate macrophage development.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.5
作者：
Kim K;Punj V;Kim JM;Lee S;Ulmer TS;Lu W;Rice JC;An W
通讯作者：
An W
影响因子：
30.8
作者：
Haney MS;Bohlen CJ;Morgens DW;Ousey JA;Barkal AA;Tsui CK;Ego BK;Levin R;Kamber RA;Collins H;Tucker A;Li A;Vorselen D;Labitigan L;Crane E;Boyle E;Jiang L;Chan J;Rincón E;Greenleaf WJ;Li B;Snyder MP;Weissman IL;Theriot JA;Collins SR;Barres BA;Bassik MC
通讯作者：
Bassik MC
影响因子：
0.8
作者：
Herrmann, Christin;Avgousti, Daphne C.;Weitzman, Matthew D.
通讯作者：
Weitzman, Matthew D.
影响因子：
158.5
作者：
De Benedetti, Fabrizio;Brunner, Hermine I.;Martini, Alberto
通讯作者：
Martini, Alberto