Co-occupancy identifies transcription factor co-operation for axon growth.
Co-occupancy identifies transcription factor co-operation for axon growth.
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DOI：
10.1038/s41467-021-22828-3
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发表时间：
2021-05-05
影响因子：
16.6
通讯作者：
Blackmore MG
中科院分区：
文献类型：
--
作者：
Venkatesh I;Mehra V;Wang Z;Simpson MT;Eastwood E;Chakraborty A;Beine Z;Gross D;Cabahug M;Olson G;Blackmore MG
转录因子（TF）是调节神经生理学的有力杠杆，可以靶向改善细胞对损伤或疾病的反应。由于TF往往依赖于合作活动，一个主要的挑战是确定和部署最佳的集合。在这里，我们开发了一个生物信息学管道，集中在TF共同占用的调控DNA，并用它来预测的因素，加强促再生Klf 6在体外的影响。高内容屏幕的神经突生长确定合作活动的12名候选人，和系统的测试在小鼠模型的皮质脊髓束（CST）损伤证实了三个新的情况下，成对合作。组合Klf 6和Nr 5a 2驱动最强的生长，并且CST神经元的转录谱确定了参与大分子生物合成和DNA修复的Klf 6/Nr 5a 2响应基因网络。这些数据确定TF组合，促进增强CST增长，澄清转录相关，并提供了一个生物信息学方法来检测TF合作。神经系统损伤后，许多神经元不能启动轴突生长所需的转录程序。在这里，作者研究了因子与调控DNA的合作结合，以预测异位共表达时改善轴突生长的组合。
Transcription factors (TFs) act as powerful levers to regulate neural physiology and can be targeted to improve cellular responses to injury or disease. Because TFs often depend on cooperative activity, a major challenge is to identify and deploy optimal sets. Here we developed a bioinformatics pipeline, centered on TF co-occupancy of regulatory DNA, and used it to predict factors that potentiate the effects of pro-regenerative Klf6 in vitro. High content screens of neurite outgrowth identified cooperative activity by 12 candidates, and systematic testing in a mouse model of corticospinal tract (CST) damage substantiated three novel instances of pairwise cooperation. Combined Klf6 and Nr5a2 drove the strongest growth, and transcriptional profiling of CST neurons identified Klf6/Nr5a2-responsive gene networks involved in macromolecule biosynthesis and DNA repair. These data identify TF combinations that promote enhanced CST growth, clarify the transcriptional correlates, and provide a bioinformatics approach to detect TF cooperation. After injury to the nervous system, many neurons fail to initiate transcriptional programs needed for axon growth. Here the authors examine co-operative binding of factors to regulatory DNA to predict combinations that improve axon growth when ectopically co-expressed.
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DOI：
10.1073/pnas.1016959108
发表时间：
2011-04-05
影响因子：
11.1
作者：
He, Aibin;Kong, Sek Won;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
8.8
作者：
Fink KL;López-Giráldez F;Kim IJ;Strittmatter SM;Cafferty WBJ
通讯作者：
Cafferty WBJ
影响因子：
3.5
作者：
Blackmore, Murray G.;Moore, Darcie L.;Smith, Robin P.;Goldberg, Jeffrey L.;Bixby, John L.;Lemmon, Vance P.
通讯作者：
Lemmon, Vance P.
影响因子：
15.9
作者：
Chen M;Zheng B
通讯作者：
Zheng B
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.