Human chromosomal region 11p15.5 contains two clusters of epigenetically-regulated genes that are expressed from only one chromosome in a parent-of-origin manner. Each cluster, or imprinted domain, is regulated by a functionally independent imprinting control region (ICR). The human CDKN1C/KCNQ1OT1 domain is regulated by an ICR located in an intron of KCNQ1, and contains at least eight genes that are expressed exclusively or preferentially from the maternally-inherited allele. The DNA of the ICR is specifically methylated on the maternally-inherited chromosome, and unmethylated on the paternally-inherited chromosome. The ICR contains the promoter of the KCNQ1OT1 gene that is exclusively expressed from the paternal allele. The KCNQ1OT1 transcript is the antisense to the KCNQ1 gene and is a unspliced long non-coding RNA. It interacts with chromatin and regulates transcription of multiple target genes through epigenetic modifications. The transcript is abnormally expressed from both chromosomes in most patients with Beckwith-Wiedemann syndrome, and the transcript also plays an important role in colorectal carcinogenesis. [provided by RefSeq, Apr 2012]
Transcription factors with Perturb-seq knockdown data for KCNQ1OT1. 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 = KCNQ1OT1 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 KCNQ1OT1, 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 |
|---|---|---|---|---|
| chr11:2,399,574–2,401,040 | 299.5 kb | Distal (>10kb) Multiome | 1060 | |
| chr11:2,420,598–2,421,164 | 279.1 kb | Distal (>10kb) Multiome | 385 | |
| chr11:2,444,173–2,445,584 | 255.1 kb | Distal (>10kb) Multiome | 280 | |
| chr11:2,532,598–2,533,458 | 167.1 kb | Distal (>10kb) Multiome | 567 | |
| chr11:2,693,272–2,694,189 | 6.5 kb | Proximal (<10kb) Multiome | 236 | |
| chr11:2,699,491–2,700,586 | 131 bp | At TSS Multiome | 879 | |
| chr11:2,700,710–2,700,891 | 707 bp | At TSS | 356 | |
| chr11:2,862,328–2,863,500 | 162.6 kb | Distal (>10kb) Multiome | 132 | |
| chr11:2,883,795–2,886,948 | 185.9 kb | Distal (>10kb) Multiome HiCAR | 639 | |
| chr11:2,891,828–2,893,111 | 192.5 kb | Distal (>10kb) Multiome | 572 | |
| chr11:2,901,621–2,903,073 | 202.2 kb | Distal (>10kb) Multiome | 610 | |
| chr11:2,928,807–2,931,249 | 230.9 kb | Distal (>10kb) Multiome | 770 | |
| chr11:2,991,519–2,993,201 | 292.4 kb | Distal (>10kb) Multiome | 759 |
Genomic view of the KCNQ1OT1 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.