The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]
Modules significantly affected by knockdown. ↑ Up = module upregulated upon KD; ↓ Down = module downregulated upon KD.
| Cluster | Dir | NES | padj | Bind | OR | padj (bind) |
|---|
| Module | Dir | NES | #gRNA | padj | Bind | OR | padj (bind) |
|---|
| Submodule | Module | Dir | NES | #gRNA | Bind | OR | padj (bind) |
|---|
Genes likely regulated by SMAD3 through linked binding evidence in open chromatin. The chart ranks TF-linked genes by their mean Perturb-seq response to SMAD3 knockdown, with negative coefficients indicating downregulation and positive coefficients indicating upregulation upon knockdown.
Open chromatin elements (ATAC-seq) where SMAD3 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 SMAD3. 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 = SMAD3 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 SMAD3, 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 |
|---|---|---|---|---|
| chr15:66,773,918–66,774,633 | 291.1 kb | Distal (>10kb) Multiome | 524 | |
| chr15:66,842,072–66,842,664 | 222.9 kb | Distal (>10kb) Multiome | 519 | |
| chr15:66,842,765–66,843,830 | 222.3 kb | Distal (>10kb) Multiome | 413 | |
| chr15:66,923,439–66,924,007 | 141.9 kb | Distal (>10kb) Multiome | 191 | |
| chr15:66,927,757–66,928,460 | 137.3 kb | Distal (>10kb) Multiome | 77 | |
| chr15:67,029,958–67,030,628 | 35.1 kb | Distal (>10kb) Multiome | 394 | |
| chr15:67,063,703–67,064,666 | 1.3 kb | Proximal (<10kb) Multiome HiCAR | 769 | |
| chr15:67,064,798–67,066,190 | 27 bp | At TSS Multiome HiCAR | 881 | |
| chr15:67,067,506–67,068,588 | 2.6 kb | Proximal (<10kb) Multiome HiCAR | 341 | |
| chr15:67,070,163–67,070,402 | 6.4 kb | Proximal (<10kb) | 48 | |
| chr15:67,071,011–67,071,208 | 7.2 kb | Proximal (<10kb) | 30 | |
| chr15:67,086,180–67,086,640 | 20.8 kb | Distal (>10kb) Multiome HiCAR | 143 | |
| chr15:67,152,836–67,153,778 | 87.7 kb | Distal (>10kb) Multiome | 90 | |
| chr15:67,164,757–67,165,266 | 99.2 kb | Distal (>10kb) Multiome HiCAR | 99 | |
| chr15:67,165,558–67,166,225 | 100.3 kb | Distal (>10kb) Multiome | 151 | |
| chr15:67,254,178–67,255,165 | 189.1 kb | Distal (>10kb) Multiome | 964 | |
| chr15:67,267,516–67,268,376 | 202.3 kb | Distal (>10kb) Multiome | 61 |
Genomic view of the SMAD3 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.