Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]
Transcription factors with Perturb-seq knockdown data for PSEN1. 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 = PSEN1 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 PSEN1, 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 |
|---|---|---|---|---|
| chr14:72,893,140–72,894,397 | 242.2 kb | Distal (>10kb) Multiome | 484 | |
| chr14:72,925,756–72,927,231 | 210.1 kb | Distal (>10kb) Multiome | 799 | |
| chr14:73,026,575–73,027,593 | 109.3 kb | Distal (>10kb) Multiome | 727 | |
| chr14:73,058,025–73,059,316 | 78.0 kb | Distal (>10kb) Multiome | 949 | |
| chr14:73,125,023–73,126,032 | 11.0 kb | Distal (>10kb) Multiome | 131 | |
| chr14:73,136,098–73,137,113 | 42 bp | At TSS Multiome | 737 | |
| chr14:73,168,802–73,169,764 | 32.8 kb | Distal (>10kb) Multiome | 44 | |
| chr14:73,235,444–73,236,071 | 99.3 kb | Distal (>10kb) Multiome | 85 | |
| chr14:73,237,315–73,238,355 | 101.4 kb | Distal (>10kb) Multiome | 296 |
Genomic view of the PSEN1 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.