Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or 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 act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided by RefSeq, Jul 2008]
Transcription factors with Perturb-seq knockdown data for PSEN2. 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 = PSEN2 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 PSEN2, 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 |
|---|---|---|---|---|
| chr1:226,608,563–226,609,002 | 261.8 kb | Distal (>10kb) Multiome HiCAR | 148 | |
| chr1:226,679,874–226,680,709 | 190.4 kb | Distal (>10kb) Multiome | 422 | |
| chr1:226,736,695–226,739,072 | 133.2 kb | Distal (>10kb) Multiome HiCAR | 426 | |
| chr1:226,824,867–226,826,112 | 45.3 kb | Distal (>10kb) Multiome | 167 | |
| chr1:226,827,950–226,828,394 | 42.4 kb | Distal (>10kb) Multiome | 514 | |
| chr1:226,870,257–226,871,262 | 71 bp | At TSS Multiome | 692 | |
| chr1:226,939,374–226,940,917 | 69.5 kb | Distal (>10kb) Multiome | 1091 | |
| chr1:226,944,823–226,946,056 | 75.0 kb | Distal (>10kb) Multiome | 574 |
Genomic view of the PSEN2 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.