HDAC inhibitor induces RAG transcription in sensory neurons.

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HDAC inhibitor induces RAG transcription in sensory neurons. HDAC inhibitor induces RAG transcription in sensory neurons. A, Western blot images and quantification of AcH4 levels in L4–L6 DRGs from vehicle, TSA, or MS-275-treated mice. B, C, Representative immunofluorescence images of DRGs from vehicle-, TSA-, or MS-275-treated mice with coimmunostaining of AcH4 (red) and neuronal markers β-tubulin (Tuj1) or NeuN (green). Scale bar, 100 μm. D, Quantitative PCR results of chromatin immunoprecipitated with AcH4 antibody at the promoter (left) or internal coding region (right) of RAGs and housekeeping genes (Gapdh and Rpl13a) in freshly dissected DRGs 6 h after the last of the 4 daily injections of vehicle or MS-275. E, qRT-PCR results of RAGs in mRNA extracts from DRGs of the same animals as in D (n = 3 independent experiments). F,G, qRT-PCR results of RAGs in mRNA extracts from DRGs of MS-275- or vehicle-treated mice (F). Of a total of 25 RAGs tested (18 shown in F plus 7 shown in E), 48% were not affected by MS-275 treatment (no change). A total of 40% exhibited same direction of transcriptional changes after MS-275 treatment compared with a conditioning lesion (concordant change), whereas 12% exhibited opposite direction of transcriptional changes (discordant change) (G). Data represent mean ± SEM. *p < 0.05. **p < 0.01. ***p < 0.001. Mattéa J. Finelli et al. J. Neurosci. 2013;33:19664-19676 ©2013 by Society for Neuroscience