Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape.
Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape.
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通过氧化应激进行转录重编程发生在预定义的染色质可及性景观中。
DOI：
10.1016/j.freeradbiomed.2021.05.016
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发表时间：
2021-08-01
影响因子：
7.4
通讯作者：
Slattery M
中科院分区：
文献类型：
--
作者：
Levings DC;Lacher SE;Palacios-Moreno J;Slattery M
活性氧(ROS)是许多生理过程中的重要信号分子，但过量的ROS会导致细胞损伤并导致病理改变。因此，细胞需要维持对ROS水平的严格调控，而ROS响应的转录重编程是这一过程的核心。尽管人们早就认识到氧化应激会导致基因表达的快速而显著的变化，但氧化应激对潜在的染色质可及性格局的影响仍不清楚。在这里，我们询问了ROS反应的转录重编程是否伴随着MCF7人乳腺癌细胞染色质环境的重编程。利用对多种氧化应激诱导剂的时程暴露，我们确定了ROS诱导的广泛的ROS反应基因表达的变化，而对染色质环境的改变最小。虽然我们确实观察到染色质可及性的变化，但这些变化是：(1)远低于氧化应激后基因表达的变化，以及(2)发生在可及染色质的预先存在的区域内。我们的ATAC-SEQ实验的Tf足迹分析确定了5个Tf或Tf家族，它们有证据表明DNA结合中存在ROS反应的变化：Nrf2、AP-1、P53、NFY和SP/KLF。重要的是，这些因子中的几个(AP-1、NF-Y和SP/KLF因子)以前没有被认为是ROS反应中的广泛调节因子。综上所述，我们已经表征了响应ROS处理的MCF7细胞在基因表达和染色质可及性方面的全基因组变化，我们发现对过量ROS的大规模转录反应的调节主要受到细胞原有染色质环境的限制。
Reactive oxygen species (ROS) are important signalling molecules in many physiological processes, yet excess ROS leads to cell damage and can lead to pathology. Accordingly, cells need to maintain tight regulation of ROS levels, and ROS-responsive transcriptional reprogramming is central to this process. Although it has long been recognized that oxidative stress leads to rapid, significant changes in gene expression, the impact of oxidative stress on the underlying chromatin accessibility landscape remained unclear. Here, we asked whether ROS-responsive transcriptional reprogramming is accompanied by reprogramming of the chromatin environment in MCF7 human breast cancer cells. Using a time-course exposure to multiple inducers of oxidative stress, we determined that the widespread ROS-responsive changes in gene expression induced by ROS occur with minimal changes to the chromatin environment. While we did observe changes in chromatin accessibility, these changes were: (1) far less numerous than gene expression changes after oxidative stress, and (2) occur within pre-existing regions of accessible chromatin. TF footprinting analysis of our ATAC-seq experiments identified 5 TFs or TF families with evidence for ROS-responsive changes in DNA binding: NRF2, AP-1, p53, NFY, and SP/KLF. Importantly, several of these (AP-1, NF-Y, and SP/KLF factors) have not been previously implicated as widespread regulators in the response to ROS. In summary, we have characterized genome-wide changes in gene expression and chromatin accessibility in response to ROS treatment of MCF7 cells, and we have found that regulation of the large-scale transcriptional response to excess ROS is primarily constrained by the cell’s pre-existing chromatin landscape.
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影响因子：
4.7
作者：
al Taleb, Zukaa;Petry, Andreas;Chi, Tabughang Franklin;Mennerich, Daniela;Goerlach, Agnes;Dimova, Elitsa Y.;Kietzmann, Thomas
通讯作者：
Kietzmann, Thomas
DOI：
10.1073/pnas.0711961105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Feng, Ru;Desbordes, Sabrina C.;Graf, Thomas
通讯作者：
Graf, Thomas
影响因子：
4.4
作者：
Gu Z;Eils R;Schlesner M;Ishaque N
通讯作者：
Ishaque N
影响因子：
7.8
作者：
Gambino V;De Michele G;Venezia O;Migliaccio P;Dall'Olio V;Bernard L;Minardi SP;Della Fazia MA;Bartoli D;Servillo G;Alcalay M;Luzi L;Giorgio M;Scrable H;Pelicci PG;Migliaccio E
通讯作者：
Migliaccio E
影响因子：
56.9
作者：
ABATE, C;PATEL, L;CURRAN, T
通讯作者：
CURRAN, T