BIOBRIEF
Salk and Arc researchers tracked two epigenetic layers — chemical tags on DNA and the 3D folding that brings distant stretches into contact — across 16 human tissues, and found the two sometimes disagree about a cell's identity.
Salk Institute and Arc Institute researchers have built the first body-wide single-cell atlas that watches DNA's 3D folding and its chemical methylation tags at the same time. The atlas spans 86,689 cells drawn from 16 human tissues, and the two "on/off" layers often disagree about what a cell is.
The atlas is a public reference resource, freely available through the NIH 4D Nucleome Data Portal, for figuring out which cell types are most exposed to disease-linked genetic variants, not a diagnostic or therapy. The work, published in Science, is the anchor of a nine-paper 4DN package: six Science papers and three in Science Advances. It resolves 35 major cell types and 206 subtypes.
Methylation is chemical tagging that tells a gene to stay quiet; 3D genome organization is the looping and folding that brings distant stretches of DNA into contact. Both are epigenetic layers: instructions written on the same DNA that distinguish, say, a neuron from a liver cell.
The two layers usually agree on a cell's identity. When they don't, the atlas offers a starting point for asking which cell types are most exposed to a given disease-linked variant, most of which sit in noncoding DNA where 3D folding controls which genes a variant can reach.
Disentangling real disagreement from measurement noise is the next step.