The protein encoded by this gene belongs to a class of eukaryotic CX(9)C proteins characterized by four cysteine residues spaced ten amino acids apart from one another. These residues form disulfide linkages that define a CHCH fold. In response to stress, the protein translocates from the mitochondrial intermembrane space to the nucleus where it binds to a highly conserved 13 nucleotide oxygen responsive element in the promoter of cytochrome oxidase 4I2, a subunit of the terminal enzyme of the electron transport chain. In concert with recombination signal sequence-binding protein J, binding of this protein activates the oxygen responsive element at four percent oxygen. In addition, it has been shown that this protein is a negative regulator of mitochondria-mediated apoptosis. In response to apoptotic stimuli, mitochondrial levels of this protein decrease, allowing BCL2-associated X protein to oligomerize and activate the caspase cascade. Pseudogenes of this gene are found on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
Transcription factors with Perturb-seq knockdown data for CHCHD2. 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 = CHCHD2 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 CHCHD2, 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 |
|---|---|---|---|---|
| chr7:55,886,966–55,887,754 | 219.0 kb | Distal (>10kb) Multiome | 546 | |
| chr7:55,951,547–55,952,549 | 154.6 kb | Distal (>10kb) Multiome | 801 | |
| chr7:55,964,099–55,965,278 | 141.8 kb | Distal (>10kb) Multiome | 738 | |
| chr7:56,033,660–56,034,707 | 72.3 kb | Distal (>10kb) Multiome | 673 | |
| chr7:56,051,159–56,052,300 | 54.8 kb | Distal (>10kb) Multiome | 882 | |
| chr7:56,063,656–56,065,393 | 42.2 kb | Distal (>10kb) Multiome | 926 | |
| chr7:56,074,109–56,074,780 | 32.0 kb | Distal (>10kb) Multiome | 423 | |
| chr7:56,106,168–56,106,786 | 89 bp | At TSS Multiome | 866 |
Genomic view of the CHCHD2 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.