Journal: The Journal of Biological Chemistry
Article Title: Cannabinoid CB2 receptors are upregulated via bivalent histone modifications and control primary afferent input to the spinal cord in neuropathic pain
doi: 10.1016/j.jbc.2022.101999
Figure Lengend Snippet: Nerve injury alters activating and repressive histone modifications at the Cnr2 promoter in the DRG. A , top , schematic representation of the rat Cnr2 gene exon and intron composition of different transcript variants. The coding sequence (starting with ATG) of the same 360 amino acid (aa) long CB2 protein (rCB2A) is localized solely within the common Exon 2 of both transcript variant 1 and variant 2. Transcript variant 3 (Exon 1–3), although 100% identical to Exon 2, encodes a longer (410 aa) CB2 protein (rCB2B). Bottom , alignment of rat CB2 protein isoforms with corresponding human (hCB2) and mouse (mCB2) isoforms shows the presence of a distinct C-terminal sequence in the rCB2B isoform, whereas the rCB2A isoform shares a high degree of similarity with hCB2 and mCB2. B , real-time qPCR analysis of Cnr2 mRNA levels using specific primers for each indicated Exon in rat DRG tissues 21 days after sham or SNL surgery. Data are expressed as mean ± SEM (n = 6 independent experiments; p < 0.0001, F(5,30) = 53.36). ∗∗∗ p < 0.001 compared with the sham group of Exon 1 (one-way ANOVA followed by Dunnett’s post hoc test). C , ChIP-qPCR quantification shows the enrichment of histone marks at -463 bp to -373 bp, -115 bp to -15 bp, -53 bp to +28 bp, and +117 bp to +219 bp regions flanking the transcription start site of the rat Cnr2 gene on chromosome 5. DRG tissues were obtained from rats 21 days after sham or SNL surgery and subjected to ChIP-qPCR to quantify the immunoprecipitated DNA using the antibodies against H3K9ac, H3K4me3, H3K9me2, H3K27me3, and pan-histone H3. The percentage of their enrichment at each indicated region on the Cnr2 promoter was normalized to the input sample and corrected with that of pan-histone H3 values. Rabbit IgG was used as a negative control in immunoprecipitations. The rat negative control primers spanning a gene desert on rat chromosome 3 was used to confirm the specificity of ChIP-qPCR. Data are expressed as means ± SEM (n = 6 independent experiments per group; DRG tissues from three rats were pooled as one sample). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, compared with the sham group (two-tailed Student’s t test). CB2, Type-2 cannabinoid receptors; ChIP-qPCR, chromatin immunoprecipitation–quantitative PCR; DRG, dorsal root ganglion; SNL, spinal nerve ligation.
Article Snippet: The membrane was incubated with blocking solution (5% nonfat dry milk in Tris-buffered saline and 0.05% Tween 20 (TBST)) at 22 °C for 1 h and then incubated overnight at 4 °C with an anti-rabbit CB2 antibody (1:200 dilution, #101550, Cayman Chemicals) diluted with TBST containing 3% bovine serum albumin.
Techniques: Sequencing, Variant Assay, ChIP-qPCR, Immunoprecipitation, Negative Control, Two Tailed Test, Chromatin Immunoprecipitation, Real-time Polymerase Chain Reaction, Ligation