Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration.
Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration.
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DOI：
10.1038/s41598-021-94341-y
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发表时间：
2021-07-21
影响因子：
4.6
通讯作者：
Cavalli V
中科院分区：
文献类型：
--
作者：
Pita-Thomas W;Gonçalves TM;Kumar A;Zhao G;Cavalli V
Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin regions that are enriched in rat embryonic RGCs (high axon growth capacity) compared to postnatal RGCs (low axon growth capacity). We found that developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the regions of the chromatin that were more accessible in embryonic RGCs. Proteomic analysis of purified rat RGC nuclei confirmed the expression of TFs with potential role in axon growth such as CREB, CTCF, YY1, and JUND. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon regeneration. Consistently, overexpression of CREB fused to the VP64 transactivation domain in mouse RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
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：
16.2
作者：
Gao, Y;Deng, KW;Filbin, MT
通讯作者：
Filbin, MT
DOI：
10.1016/j.biocel.2014.04.018
发表时间：
2014-11-01
影响因子：
4
作者：
Hellstroem, Mats;Harvey, Alan R.
通讯作者：
Harvey, Alan R.