HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Transcription factors with Perturb-seq knockdown data for HMGCR. 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 = HMGCR 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 HMGCR, 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 |
|---|---|---|---|---|
| chr5:75,052,462–75,054,650 | 283.5 kb | Distal (>10kb) Multiome HiCAR | 602 | |
| chr5:75,198,716–75,199,683 | 138.2 kb | Distal (>10kb) Multiome | 16 | |
| chr5:75,199,928–75,200,428 | 137.0 kb | Distal (>10kb) Multiome | 39 | |
| chr5:75,236,392–75,237,296 | 100.3 kb | Distal (>10kb) Multiome | 744 | |
| chr5:75,330,225–75,330,743 | 6.5 kb | Proximal (<10kb) | 15 | |
| chr5:75,336,144–75,337,997 | 176 bp | At TSS Multiome | 912 | |
| chr5:75,465,632–75,466,823 | 129.3 kb | Distal (>10kb) Multiome | 201 | |
| chr5:75,510,698–75,512,248 | 174.6 kb | Distal (>10kb) Multiome | 941 | |
| chr5:75,610,714–75,612,105 | 274.5 kb | Distal (>10kb) Multiome | 445 |
Genomic view of the HMGCR 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.