Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland, United States of America.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
PLoS Biol. 2018 Sep 10;16(9):e2006347. doi: 10.1371/journal.pbio.2006347. eCollection 2018 Sep.
Transcription factor nuclear factor kappa B (NF-κB) regulates cellular responses to environmental cues. Many stimuli induce NF-κB transiently, making time-dependent transcriptional outputs a fundamental feature of NF-κB activation. Here we show that NF-κB target genes have distinct kinetic patterns in activated B lymphoma cells. By combining RELA binding, RNA polymerase II (Pol II) recruitment, and perturbation of NF-κB activation, we demonstrate that kinetic differences amongst early- and late-activated RELA target genes can be understood based on chromatin configuration prior to cell activation and RELA-dependent priming, respectively. We also identified genes that were repressed by RELA activation and others that responded to RELA-activated transcription factors. Cumulatively, our studies define an NF-κB-responsive inducible gene cascade in activated B cells.
转录因子核因子 kappa B(NF-κB)调节细胞对环境信号的反应。许多刺激物短暂诱导 NF-κB,使时间依赖性转录输出成为 NF-κB 激活的基本特征。在这里,我们表明 NF-κB 靶基因在激活的 B 淋巴瘤细胞中有不同的动力学模式。通过结合 RELA 结合、RNA 聚合酶 II(Pol II)募集以及 NF-κB 激活的干扰,我们证明早期和晚期激活的 RELA 靶基因之间的动力学差异可以基于细胞激活前的染色质构象和 RELA 依赖性启动分别来理解。我们还鉴定了受 RELA 激活抑制的基因和对 RELA 激活的转录因子有反应的基因。总之,我们的研究定义了激活的 B 细胞中 NF-κB 反应性诱导基因级联。