The protein encoded by this intronless gene belongs to the iodothyronine deiodinase family. It catalyzes the inactivation of thyroid hormone by inner ring deiodination of the prohormone thyroxine (T4) and the bioactive hormone 3,3',5-triiodothyronine (T3) to inactive metabolites, 3,3',5'-triiodothyronine (RT3) and 3,3'-diiodothyronine (T2), respectively. This enzyme is highly expressed in pregnant uterus, placenta, fetal and neonatal tissues, and thought to prevent premature exposure of developing fetal tissues to adult levels of thyroid hormones. It regulates circulating fetal thyroid hormone concentrations, and thus plays a critical role in mammalian development. Knockout mice lacking this gene exhibit abnormalities related to development and reproduction, and increased activity of this enzyme in infants with hemangiomas causes severe hypothyroidism. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. [provided by RefSeq, May 2016]
Transcription factors with Perturb-seq knockdown data for DIO3. 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 = DIO3 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 DIO3, 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 |
|---|---|---|---|---|
| chr14:100,904,412–100,905,040 | 655.5 kb | Distal (>10kb) Multiome HiCAR | 121 | |
| chr14:101,183,321–101,183,789 | 376.6 kb | Distal (>10kb) Multiome HiCAR | 167 | |
| chr14:101,310,915–101,311,513 | 249.0 kb | Distal (>10kb) Multiome | 8 | |
| chr14:101,458,642–101,459,586 | 100.9 kb | Distal (>10kb) Multiome | 189 | |
| chr14:101,559,493–101,562,183 | 1.3 kb | Proximal (<10kb) Multiome | 329 | |
| chr14:101,563,518–101,564,657 | 3.9 kb | Proximal (<10kb) Multiome | 127 | |
| chr14:101,564,868–101,565,264 | 4.7 kb | Proximal (<10kb) | 120 | |
| chr14:101,688,293–101,688,782 | 128.4 kb | Distal (>10kb) Multiome | 137 | |
| chr14:101,705,720–101,706,457 | 146.0 kb | Distal (>10kb) Multiome | 326 | |
| chr14:101,726,532–101,727,181 | 166.7 kb | Distal (>10kb) Multiome | 45 | |
| chr14:101,760,098–101,762,537 | 201.6 kb | Distal (>10kb) Multiome | 852 | |
| chr14:101,809,684–101,810,434 | 249.9 kb | Distal (>10kb) Multiome | 701 |
Genomic view of the DIO3 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.