免疫球蛋白类转换
转录因子
生殖系
抄写(语言学)
细胞生物学
生物
泛素
化学
遗传学
基因
抗体
B细胞
语言学
哲学
作者
Bo Zhao,Zhigang Xia,Binyao Yang,Yinglu Guo,Ruizhi Zhou,Mingyu Gu,Meiling Liu,Qingcheng Li,Wanyu Bai,Junbin Huang,Xuefei Zhang,Chen Zhu,Kam Tong Leung,Chun Chen,Jing Dong
出处
期刊:Cell Reports
[Elsevier]
日期:2024-05-01
卷期号:43 (5): 114194-114194
标识
DOI:10.1016/j.celrep.2024.114194
摘要
Class switch recombination (CSR) diversifies the effector functions of antibodies and involves complex regulation of transcription and DNA damage repair. Here, we show that the deubiquitinase USP7 promotes CSR to immunoglobulin A (IgA) and suppresses unscheduled IgG switching in mature B cells independent of its role in DNA damage repair, but through modulating switch region germline transcription. USP7 depletion impairs Sα transcription, leading to abnormal activation of Sγ germline transcription and increased interaction with the CSR center via loop extrusion for unscheduled IgG switching. Rescue of Sα transcription by transforming growth factor β (TGF-β) in USP7-deleted cells suppresses Sγ germline transcription and prevents loop extrusion toward IgG CSR. Mechanistically, USP7 protects transcription factor RUNX3 from ubiquitination-mediated degradation to promote Sα germline transcription. Our study provides evidence for active transcription serving as an anchor to impede loop extrusion and reveals a functional interplay between USP7 and TGF-β signaling in promoting RUNX3 expression for efficient IgA CSR.
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