Cellular zinc status alters chromatin accessibility and binding of p53 to DNA.
Daniel OcampoLeah J DamonLynn SanfordSamuel E HoltzenTaylor JonesMary A AllenRobin D DowellAmy E PalmerPublished in: Life science alliance (2024)
Zn 2+ is an essential metal required by approximately 850 human transcription factors. How these proteins acquire their essential Zn 2+ cofactor and whether they are sensitive to changes in the labile Zn 2+ pool in cells remain open questions. Using ATAC-seq to profile regions of accessible chromatin coupled with transcription factor enrichment analysis, we examined how increases and decreases in the labile zinc pool affect chromatin accessibility and transcription factor enrichment. We found 685 transcription factor motifs were differentially enriched, corresponding to 507 unique transcription factors. The pattern of perturbation and the types of transcription factors were notably different at promoters versus intergenic regions, with zinc-finger transcription factors strongly enriched in intergenic regions in elevated Zn 2+ To test whether ATAC-seq and transcription factor enrichment analysis predictions correlate with changes in transcription factor binding, we used ChIP-qPCR to profile six p53 binding sites. We found that for five of the six targets, p53 binding correlates with the local accessibility determined by ATAC-seq. These results demonstrate that changes in labile zinc alter chromatin accessibility and transcription factor binding to DNA.
Keyphrases
- transcription factor
- dna binding
- genome wide
- heavy metals
- oxide nanoparticles
- single cell
- genome wide identification
- rna seq
- endothelial cells
- induced apoptosis
- cell free
- gene expression
- circulating tumor
- minimally invasive
- oxidative stress
- dna damage
- high throughput
- single molecule
- risk assessment
- nucleic acid
- endoplasmic reticulum stress