The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]
Modules significantly affected by knockdown. ↑ Up = module upregulated upon KD; ↓ Down = module downregulated upon KD.
| Module | Dir | NES | #gRNA | padj | Bind | OR | padj (bind) |
|---|
| Submodule | Module | Dir | NES | #gRNA | Bind | OR | padj (bind) |
|---|
Genes likely regulated by TGIF1 through linked binding evidence in open chromatin. The chart ranks TF-linked genes by their mean Perturb-seq response to TGIF1 knockdown, with negative coefficients indicating downregulation and positive coefficients indicating upregulation upon knockdown.
Open chromatin elements (ATAC-seq) where TGIF1 has ChIP-seq or motif footprint binding evidence and which are linked to at least one target gene region.
| Element | Size | Linked genes |
|---|
Transcription factors with Perturb-seq knockdown data for TGIF1. 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 = TGIF1 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 TGIF1, 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 |
|---|---|---|---|---|
| chr18:3,245,709–3,246,515 | 201.5 kb | Distal (>10kb) Multiome | 627 | |
| chr18:3,246,619–3,248,313 | 200.1 kb | Distal (>10kb) Multiome | 1018 | |
| chr18:3,261,342–3,262,799 | 185.6 kb | Distal (>10kb) Multiome | 929 | |
| chr18:3,296,788–3,297,724 | 150.2 kb | Distal (>10kb) Multiome HiCAR | 828 | |
| chr18:3,346,756–3,347,972 | 100.3 kb | Distal (>10kb) Multiome | 44 | |
| chr18:3,446,640–3,446,951 | 656 bp | At TSS | 196 | |
| chr18:3,447,486–3,448,604 | 625 bp | At TSS Multiome | 938 | |
| chr18:3,448,748–3,450,993 | 2.4 kb | Proximal (<10kb) Multiome | 909 | |
| chr18:3,451,419–3,452,004 | 3.8 kb | Proximal (<10kb) | 608 | |
| chr18:3,453,995–3,454,399 | 6.4 kb | Proximal (<10kb) | 330 | |
| chr18:3,454,708–3,454,964 | 7.1 kb | Proximal (<10kb) | 247 | |
| chr18:3,498,885–3,499,424 | 51.7 kb | Distal (>10kb) Multiome | 144 | |
| chr18:3,553,601–3,555,390 | 106.7 kb | Distal (>10kb) Multiome HiCAR | 275 | |
| chr18:3,593,642–3,595,153 | 146.5 kb | Distal (>10kb) Multiome HiCAR | 832 | |
| chr18:3,602,775–3,604,355 | 155.7 kb | Distal (>10kb) Multiome HiCAR | 903 | |
| chr18:3,610,182–3,610,667 | 162.8 kb | Distal (>10kb) Multiome HiCAR | 99 | |
| chr18:3,665,799–3,666,586 | 218.6 kb | Distal (>10kb) Multiome HiCAR | 692 |
Genomic view of the TGIF1 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.