Fig 1: HDAC7 compensatory overexpression is induced by JUN.(A) ChIP-qPCR of dbcAMP treated rat Schwann cells with anti-JUN antibody showed that this transcription factor is bound to the promoter of Hdac7. Four different experiments from four distinct cultures were used. Data were analyzed with the Mann–Whitney test. (B) A 1.189 fragment of the mouse Hdac7 promoter containing a conserved JUN binding consensus sequence was PCR amplified and cloned into the pGL3 luciferase reporter vector. HEK293 cells were transfected with this construct and the pcDNA3 (empty vector) or pcDNA3 Jun. As is shown JUN induced the luciferase activity by 3.4 ± 0.22-fold (p < 0.0001; n = 10). Unpaired t-test with Welch’s correlation was used for statistical comparison. (C) Levels of mRNA for Jun in the nerves of Jun_OE and Jun_cKO mice. (D) Hdac7 expression is enhanced in the sciatic nerves of the Jun_OE mice (5.16 ± 0.46 × 10-5 in the Jun_OE versus 3.09 ± 0.29 × 10-5 in the WT; p = 0.005) but does not change in the Jun_cKO mice. (E) Hdac4 expression in sciatic nerves does not change in Jun_OE and Jun_cKO mice. (F) Hdac5 expression in sciatic nerves does not change in Jun_OE and Jun_cKO mice. (G) Removal of Jun from Schwann cells in the dKO (dKO;Jun_cKO genotype) prevents Hdac7 compensatory overexpression. Interestingly, Hdac9 expression is induced in these mice (see discussion). RT-qPCR with mouse-specific primers for the indicated genes was performed. The scatter plot, which include also the mean ± standard error (SE), shows the expression of each gene normalized to the housekeeping 18S. Four to five mice per genotype were used. Data were analyzed with the unpaired t-test with Welch’s correlation. (H) A peak of HDAC4 (NA_peak 3487) was found on the Hdac7 promoter in the ChIP-Seq experiemt. (I) ChIP-qPCR confirmed that HDAC4 is bound to the promoter of Hdac7. Four different experiments from four distinct cultures were used. Data were analyzed with the Mann–Whitney test (*p < 0.05; **p < 0.01; ***p < 0.001; ns: no significant). See source data file one online (graphs source data) for more details.