The Bromodomain Containing 8 (BRD8) transcriptional network in human lung epithelial cells.
The Bromodomain Containing 8 (BRD8) transcriptional network in human lung epithelial cells.
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DOI：
10.1016/j.mce.2021.111169
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发表时间：
2021-03-15
影响因子：
4.1
通讯作者：
Harris A
中科院分区：
文献类型：
--
作者：
Browne JA;NandyMazumdar M;Paranjapye A;Leir SH;Harris A
调节气道上皮基因表达的机制是其对环境的反应的基础。转录因子（TF）和结构蛋白的网络，调节染色质可及性并募集激活或抑制信号。含溴结构域蛋白质作为TF或通过参与甲基转移酶或乙酰转移酶活性来诱导染色质修饰。在这里，我们研究了含溴结构域8（BRD 8）在协调肺上皮功能中的作用。在人肺上皮细胞系（Calu-3和16 HBE 140-）中定位BRD 8全基因组占据位点。基于BRD 8 ChIP-seq峰下的基序过度表达，CCCTC结合因子（CTCF）被鉴定为BRD 8的预测辅因子。在siRNA介导的BRD 8耗尽后，对具有BRD 8占据峰附近的差异表达基因进行基因本体过程富集分析。BRD 8靶标富含参与先天免疫应答和细胞周期的基因。BRD 8的消耗增加了抗菌肽β-防御素1和多种趋化因子的分泌，并降低了细胞增殖。
Mechanisms regulating gene expression in the airway epithelium underlie its response to the environment. A network of transcription factors (TFs) and architectural proteins, modulate chromatin accessibility and recruit activating or repressive signals. Bromodomain-containing proteins function as TFs or by engaging methyltransferase or acetyltransferase activity to induce chromatin modifications. Here we investigate the role of Bromodomain Containing 8 (BRD8) in coordinating lung epithelial function. Sites of BRD8 occupancy genome-wide were mapped in human lung epithelial cell lines (Calu-3 and 16HBE14o-). CCCTC-Binding Factor (CTCF) was identified as a predicted co-factor of BRD8, based upon motif over-representation under BRD8 ChIP-seq peaks. Following siRNA-mediated depletion of BRD8, differentially expressed genes with nearby peaks of BRD8 occupancy were subject to gene ontology process enrichment analysis. BRD8 targets are enriched for genes involved in the innate immune response and the cell cycle. Depletion of BRD8 increased the secretion of the antimicrobial peptide beta-defensin 1 and multiple chemokines, and reduced cell proliferation.
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影响因子：
16
作者：
Hsu SC;Gilgenast TG;Bartman CR;Edwards CR;Stonestrom AJ;Huang P;Emerson DJ;Evans P;Werner MT;Keller CA;Giardine B;Hardison RC;Raj A;Phillips-Cremins JE;Blobel GA
通讯作者：
Blobel GA
影响因子：
10.5
作者：
Gevry, Nicolas;Hardy, Sara;Gaudreau, Luc
通讯作者：
Gaudreau, Luc
影响因子：
4.8
作者：
Fossum, Sara L.;Mutolo, Michael J.;Harris, Ann
通讯作者：
Harris, Ann
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
影响因子：
2
作者：
Hosoya, Takeshi;Monden, Tsuyoshi;Mori, Masatomo
通讯作者：
Mori, Masatomo