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. 2018 Nov 13;12:808. doi: 10.3389/fnins.2018.00808

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Copyright © 2018 Tica and Didangelos.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The transcription factor SP1 likely controls a large number of differentially regulated genes in rats and axolotls. (A) Transcription factors with the highest number of likely promoter binding sites. Transcription factor mining was performed with MSigDB. This tool counts genes having one or more occurrences of transcription factor binding sites in regions spanning 4 kb around their transcription starting sites. SP1 was the transcription factor with the highest number of likely hits and lowest adjusted p-value for genes that were consistently upregulated in rats but consistently downregulated in axolotls at days 1, 3, and 7 post-SCI. (B) SP1 gene expression was increased in rats after SCI but was unchanged in axolotls at days 1, 3, and 7 post-SCI. The graph depicts the average (days 1, 3, and 7) log fold-change in the expression of SP1 from the rat and axolotl microarray datasets. Rat and axolotl SP1 sequences share a 65% identity and 78% similarity. (C) Principal component analysis of all differentially regulated genes in rats and axolotls highlighting the genes that were predicted by MSigDB to contain SP1 promoter binding sites. Magenta highlights rat SP1-controlled genes while blue highlights axolotl SP1-controlled genes. (D) Protein-protein interaction network of 316 SP1-regulated genes and 284 SP1 1st neighbor genes (see Supplemental Figures 5A–C). All 514 genes are upregulated after rat SCI at day 1, 3, and 7. SP1 is highlighted as a yellow node. (E) The SP1-related genes shown in (D) contained a tightly connected cluster of classic inflammatory response genes (“immune system process;” see Supplemental Figure 5D) visualized as a protein-protein interaction network. Note the presence of classic inflammatory response genes, signaling components and transcription factors. (F) The parallel coordinate plot visualizes the inflammatory response genes shown in (E) in rats and axolotls and how they change across the species from day 1 to day 7 (orange lines). Most of these genes are upregulated in rats but downregulated or unchanged in axolotls. SP1 is the yellow line.