The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]
Transcription factors with Perturb-seq knockdown data for MLH1. 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 = MLH1 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 MLH1, 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 |
|---|---|---|---|---|
| chr3:36,763,790–36,765,063 | 229.1 kb | Distal (>10kb) Multiome | 293 | |
| chr3:36,843,022–36,843,960 | 149.8 kb | Distal (>10kb) Multiome | 228 | |
| chr3:36,868,736–36,869,366 | 124.5 kb | Distal (>10kb) Multiome | 230 | |
| chr3:36,943,704–36,946,013 | 48.9 kb | Distal (>10kb) Multiome | 388 | |
| chr3:36,965,264–36,965,767 | 27.9 kb | Distal (>10kb) Multiome | 89 | |
| chr3:37,175,555–37,176,875 | 182.8 kb | Distal (>10kb) Multiome | 907 | |
| chr3:37,242,726–37,244,363 | 249.8 kb | Distal (>10kb) Multiome | 969 |
Genomic view of the MLH1 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.