NF-κB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells.
NF-κB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells.
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在抗原受体激活的B细胞中，核因子-κB亚基以不同的动力学方式引导转录级联反应。
DOI：
10.1038/s41590-023-01561-7
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发表时间：
2023-09
影响因子：
30.5
通讯作者：
Sen, Ranjan
中科院分区：
文献类型：
--
作者：
Zhao, Mingming;Chauhan, Prashant;Sherman, Cheryl A.;Singh, Amit;Kaileh, Mary;Mazan-Mamczarz, Krystyna;Ji, Hongkai;Joy, Jaimy;Nandi, Satabdi;De, Supriyo;Zhang, Yongqing;Fan, Jinshui;Becker, Kevin G.;Loke, Png;Zhou, Weiqiang;Sen, Ranjan
核因子κ B（NF-κB）家族的转录因子在不同的细胞类型中协调信号诱导的基因表达。对NF-κB活化的细胞应答在细胞和信号特异性水平以及家族成员的差异使用（亚基特异性）水平上受到调节。在此，我们使用时间依赖性多组学研究了两种密切相关的NF-κB蛋白Rel和RelA在通过B细胞受体活化的原代B淋巴细胞中的选择性功能。尽管在全基因组范围内有大量的共享结合位点，但Rel和RelA在活化的B细胞中指导基因表达的动力学上不同的级联反应。单细胞RNA测序显示Rel和RelA特异性反应的显著异质性，这些因子的顺序结合不是延长转录的主要机制。此外，核共表达的Rel和RelA导致的功能之间的拮抗作用的因素。通过严格鉴定每个NF-κB亚基的靶基因，这些研究提供了对Rel和RelA在免疫和癌症中的独特功能的见解。Sen等人提供了B细胞受体（BCR）激活后B细胞中核因子κ B（NF-κB）调节基因表达的单细胞RNA测序（scRNA-seq）谱的深度时间多组学分析。他们的发现揭示了RelA和Rel介导的基因表达的不同动力学模式以及密切相关的NF-κB亚基之间的功能拮抗作用。
The nuclear factor kappa B (NF-κB) family of transcription factors orchestrates signal-induced gene expression in diverse cell types. Cellular responses to NF-κB activation are regulated at the level of cell and signal specificity, as well as differential use of family members (subunit specificity). Here we used time-dependent multi-omics to investigate the selective functions of Rel and RelA, two closely related NF-κB proteins, in primary B lymphocytes activated via the B cell receptor. Despite large numbers of shared binding sites genome wide, Rel and RelA directed kinetically distinct cascades of gene expression in activated B cells. Single-cell RNA sequencing revealed marked heterogeneity of Rel- and RelA-specific responses, and sequential binding of these factors was not a major mechanism of protracted transcription. Moreover, nuclear co-expression of Rel and RelA led to functional antagonism between the factors. By rigorously identifying the target genes of each NF-κB subunit, these studies provide insights into exclusive functions of Rel and RelA in immunity and cancer. Sen et al. provide in-depth temporal multi-omic analyses with single-cell RNA-sequencing (scRNA-seq) profiles of nuclear factor kappa B (NF-κB)-regulated gene expression in B cells upon B cell receptor (BCR) activation. Their findings reveal distinct kinetic patterns of gene expression mediated by RelA and Rel and functional antagonism between the closely related NF-κB subunits.
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影响因子：
32.4
作者：
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通讯作者：
Hoffmann A
影响因子：
4.3
作者：
Boffa, DJ;Feng, B;Liou, HC
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作者：
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通讯作者：
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转录因子TFII-I微调B淋巴细胞的先天特性。
影响因子：
7.3
作者：
Singh, Amit;Kaileh, Mary;De, Supriyo;Mazan-Mamczarz, Krystyna;Bayarsaihan, Dashzeveg;Sen, Ranjan;Roy, Ananda L.
通讯作者：
Roy, Ananda L.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK