Fig 1: Additional ATXN1 interacting transcription factors regulate genes altered in SCA1(A) Proteins identified by IP-MS of ATXN1 in cerebellar tissue at 4 weeks of age and intersected with mouse transcription factors.(B) IP of ATXN1 and blotting for transcription factors CIC, RFX1, and ZBTB5 in 4-week cerebellar tissue.(C–E) (C) Comparison of available consensus motifs for RFX1, ZKSCAN1, and CIC. Jitter plot of (D) RFX1 and (E) ZKSCAN1 motif enrichment in Atxn1154Q/2Q and Atxn1154Q[V591A;S602D]/2Q DEGs by brain region. The black dot indicates % DEGs with motif within 1 kb of the transcriptional start site from each respective RNA-seq dataset. Colored jitter plot represents the % of non-DEGs with motif calculated over 10,000 random iterations.(F–I) (F) Pie charts of Atxn1154Q/2Q DEGs parsed by which contain CIC, RFX1, or ZKSCAN1 peaks analyzed across brain regions. “Multiple TFs” refers to Atxn1154Q/2Q DEGs that contain transcription factors motifs from two or more factors. Bar plots of relative normalized RNA-seq gene counts of Atxn1154Q/2Q DEGs in the cerebellum that contain a (G) CIC, (H) RFX1, or (I) ZKSCAN1 peak.(J–L) (J) Cartoon demonstrating differentiation process of SCA1 and healthy patient control iPSCs into iNeurons. Cartoon generated using Biorender.com. Bar chart demonstrating RT-qPCR RNA expression data from genes regulated by (K) RFX1 or (L) ZKSCAN1 in human iPSC-derived iNeurons. Each bar represents an original biological sample collected (2 healthy controls and 2 SCA1 patients), and each data point within the bar represents a line generated from that sample (n = 4). One-way ANOVAs with Dunnett’s multiple comparisons test were used for (G), (H), and (I). t tests were used in (K) and (L). in each case, *, **, ***, **** and ns denote p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p > 0.05, respectively. All data are represented as mean ± SEM. See also Figure S3.