The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 6, and it has been determined that the diseased allele contains 40-83 CAG repeats, compared to 6-39 in the normal allele, and is associated with spinocerebellar ataxia type 1 (SCA1). Alternative splicing results in multiple transcript variants, with one variant encoding multiple distinct proteins, ATXN1 and Alt-ATXN1, due to the use of overlapping alternate reading frames. [provided by RefSeq, Nov 2017]
Transcription factors with Perturb-seq knockdown data for ATXN1. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = ATXN1 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of ATXN1, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr6:16,331,420–16,332,565 | 429.2 kb | Distal (>10kb) Multiome HiCAR | 498 | |
| chr6:16,645,904–16,646,847 | 115.1 kb | Distal (>10kb) Multiome | 166 | |
| chr6:16,758,245–16,758,900 | 2.6 kb | Proximal (<10kb) | 233 | |
| chr6:16,759,726–16,763,021 | 259 bp | At TSS Multiome | 1093 | |
| chr6:16,763,130–16,763,384 | 1.6 kb | Proximal (<10kb) | 299 | |
| chr6:16,771,013–16,771,264 | 9.5 kb | Proximal (<10kb) | 394 | |
| chr6:16,803,203–16,804,073 | 42.1 kb | Distal (>10kb) Multiome | 270 | |
| chr6:16,858,285–16,858,924 | 97.0 kb | Distal (>10kb) Multiome | 190 | |
| chr6:16,964,738–16,965,398 | 203.6 kb | Distal (>10kb) Multiome HiCAR | 441 |
Genomic view of the ATXN1 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.