Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration.
Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration.
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神经元损伤转录反应的分析确定 CTCF 和 YY1 是调节轴突再生的协同因子。
DOI：
10.3389/fnmol.2022.967472
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发表时间：
2022
影响因子：
4.8
通讯作者：
Cavalli, Valeria
中科院分区：
文献类型：
--
作者：
Avraham, Oshri;Le, Jimmy;Leahy, Kathleen;Li, Tiandao;Zhao, Guoyan;Cavalli, Valeria
关键词：
Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of known regeneration associated transcription factors, including Jun, Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hif1α, Pparγ, Ascl1a, Srf, and Ctcf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of novel candidate transcription factors alone or in combination promotes axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis highlights that transcription factor interaction and chromatin architecture play important roles as a regulator of axon regeneration.
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影响因子：
64.5
作者：
Cho Y;Sloutsky R;Naegle KM;Cavalli V
通讯作者：
Cavalli V
影响因子：
25
作者：
Miller, Bradley R.;Press, Craig;Daniels, Richard W.;Sasaki, Yo;Milbrandt, Jeffrey;DiAntonio, Aaron
通讯作者：
DiAntonio, Aaron
影响因子：
5.3
作者：
Broude, E;McAtee, M;Bregman, BS
通讯作者：
Bregman, BS
影响因子：
7
作者：
Beagan JA;Duong MT;Titus KR;Zhou L;Cao Z;Ma J;Lachanski CV;Gillis DR;Phillips-Cremins JE
通讯作者：
Phillips-Cremins JE
影响因子：
3.4
作者：
Carlin, Dan;Halevi, Alexandra E.;Cavalli, Valeria
通讯作者：
Cavalli, Valeria