Enhancer selection dictates gene expression responses in remote organs during tissue regeneration.
Enhancer selection dictates gene expression responses in remote organs during tissue regeneration.
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DOI：
10.1038/s41556-022-00906-y
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发表时间：
2022-05
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
急性创伤刺激局部修复机制，但也可以影响远离损伤的结构，例如通过循环因子的活动。为了研究远端组织在组织再生过程中的反应，我们对实验性心脏损伤后斑马鱼大脑的转录本进行了分析。我们发现，转录因子基因cebpd除了在心外膜细胞局部诱导外，还在脑室管膜细胞和肾小管上皮细胞中远程上调。CEBPD突变改变了局部和远处的心脏损伤反应，改变了心外膜细胞的增殖以及远处液体室之间的交换。全基因组图谱和转基因鉴定发现，在cebpd附近存在一种激素反应增强子，它以允许的状态存在，使心脏损伤后心脏、脑和肾脏的基因快速表达。该序列的缺失选择性地取消了CEBPD在远程组织中的诱导，并扰乱了损伤后的液体调节，而不影响其局部心脏表达反应。我们的发现提出了一种在再生过程中拓宽基因功能的模型，在该模型中，增强子调控元件定义了对损伤的短期和长期表达反应。
Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for instance through the activity of circulating factors. To study responses of remote tissues during tissue regeneration, we profiled transcriptomes of zebrafish brains after experimental cardiac damage. We found that the transcription factor gene cebpd was upregulated remotely in brain ependymal cells as well as kidney tubular cells, in addition to its local induction in epicardial cells. cebpd mutations altered both local and distant cardiac injury responses, altering proliferation of epicardial cells as well as exchange between distant fluid compartments. Genome-wide profiling and transgenesis identified a hormone-responsive enhancer near cebpd that exists in a permissive state, enabling rapid gene expression in heart, brain, and kidney after cardiac injury. Deletion of this sequence selectively abolished cebpd induction in remote tissues and disrupted fluid regulation after injury, without affecting its local cardiac expression response. Our findings suggest a model to broaden gene function during regeneration in which enhancer regulatory elements define short- and long-range expression responses to injury.
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影响因子：
11.8
作者：
Goldman JA;Kuzu G;Lee N;Karasik J;Gemberling M;Foglia MJ;Karra R;Dickson AL;Sun F;Tolstorukov MY;Poss KD
通讯作者：
Poss KD
DOI：
10.1016/j.cub.2010.01.038
发表时间：
2010-03-09
期刊：
Current biology : CB
影响因子：
--
作者：
Halme A;Cheng M;Hariharan IK
通讯作者：
Hariharan IK
影响因子：
5
作者：
Cutie, Stephen;Payumo, Alexander Y.;Huang, Guo N.
通讯作者：
Huang, Guo N.
影响因子：
7.3
作者：
Katsu, Yoshinao;Oka, Kaori;Baker, Michael E.
通讯作者：
Baker, Michael E.
影响因子：
11.8
作者：
Kang, Junsu;Nachtrab, Gregory;Poss, Kenneth D.
通讯作者：
Poss, Kenneth D.