Principles of 3D compartmentalization of the human genome

• Published in: Cell reports (Cambridge) Vol. 35; no. 13; p. 109330
• Main Authors: Nichols, Michael H., Corces, Victor G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.06.2021; Elsevier
• Subjects: 3D organization; Animals; Cell Compartmentation - genetics; chromatin; Chromatin - metabolism; Chromosomes, Human, Pair 14 - genetics; cohesin; CTCF; Drosophila - genetics; enhancer; Genome, Human; Genome, Insect; HCT116 Cells; Histone Code - genetics; Humans; Imaging, Three-Dimensional; nucleus; transcription; Transcription, Genetic; enhancer; cohesin; transcription; 3D organization; nucleus; CTCF; chromatin
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109330

Chromatin is organized in the nucleus via CTCF loops and compartmental domains. Here, we compare different cell types to identify distinct paradigms of compartmental domain formation in human tissues. We identify and quantify compartmental forces correlated with histone modifications characteristic of transcriptional activity and previously underappreciated roles for distinct compartmental domains correlated with the presence of H3K27me3 and H3K9me3, respectively. We present a computer simulation model capable of predicting compartmental organization based on the biochemical characteristics of independent chromatin features. Using this model, we show that the underlying forces responsible for compartmental domain formation in human cells are conserved and that the diverse compartmentalization patterns seen across cell types are due to differences in chromatin features. We extend these findings to Drosophila to suggest that the same principles are at work beyond humans. These results offer mechanistic insights into the fundamental forces driving the 3D organization of the genome. [Display omitted] •Human cells have at least three distinct compartments: one active and two inactive•Compartments correlate with the presence of H3K27ac, H3K27me3, or H3K9me3•Compartmentalization principles differ between chromosomes of the same cell•Compartments are predictable from one-dimensional epigenetic information Using high-resolution Hi-C data and computer simulations, Nichols and Corces show that compartments arise as a consequence of interactions among proteins that correlate with the presence of H3K27ac, H3K27me3, and H3K9me3, suggesting that human cells contain at least three distinct compartments. The same principles apply to other organisms.