Fig. 4: Chromatin architecture at Pde10a is impaired in the striatum of HD Q140 mice.

a Scheme showing 4C-seq technique major steps using mouse striatum. PCR primers specific to each bait can be found in the “Methods” section. RE restriction enzyme. b On the left, 4C-seq profiles at Pde10a locus using HD Q140 (orange) and WT (blue) mouse striatum at 6 months. The mean of male and female 4C-seq quartile normalized read counts is plotted as the main lane for each condition. Statistical analysis of differential interacting peaks in Q140 vs WT was performed using two-paired t-test, with multiple testing correction using the Benjamini-Hochberg method. P = 0.1 (upstream of Pde10a promoter), P = 0.07 (downstream of Pde10a promoter). Gene annotations are included as well as H3K27ac ChIPseq signals (using ChIPseq data generated in this study on the striatum of Q140 and WT mice at same age). Grey shadows show specific interacting regions. On the middle, zoom into Pde10a intronic region, showing H3K27ac and H3K9me3 levels in WT and Q140 mice striatum together with CTCF enrichment (from CTCF ChIP-seq data generated in mESC). On the right, model to explain chromatin conformational changes at Pde10a locus in HD mouse striatum. c 4C-seq profiles at Pde10a locus generated using HD R6/1 (orange) and WT (blue) mouse striatum at 14 weeks of age and using mESC (green). Gene annotations and H3K27ac ChIPseq signals³ are included. Grey shadows show specific interacting regions. d 4C-seq profiles at Msh2 locus using Q140 (orange) and WT (blue) striatum at 6 months. The mean of male and female 4C-seq quartile normalized read counts is plotted as the main lane for each condition. Gene annotations and H3K27ac ChIPseq signals are included. Grey shadows show specific interacting regions. Msh6 promoter is annotated to highlight the distal chromatin loop formed with Msh2 promoter.