About 98% of the human genome encodes no proteins. But many sequences in these noncoding expanses do regulate where, when and how avidly the genes in the remaining 2% are expressed, and variations and mutations in these regions contribute enormously to disease. Active regulatory sequences are found in stretches of chromatin—the term for DNA and its protein scaffolding—that are open and accessible to the cell’s gene reading machinery, while latent sequences are bundled up and packed away. To capture how active regulatory sequences vary between cell types, a team led by Ludwig San Diego’s Bing Ren assayed chromatin accessibility in 600,000 individual cells from 30 adult human tissues to produce a single-cell chromatin atlas of the genome. The researchers then integrated that information with similar data from 15 fetal tissue types to generate a map identifying about 1.2 million regulatory DNA sequences in 222 distinct cell types. Their study, reported in Cell in November, identified the regulatory elements active in each cell type and described thousands of them associated with one or more of 240 complex human traits and diseases.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).