Polycomb "Polypacks" The Chromatin

For decades, researchers have made a tremendous effort to characterize the chromosome organization in the nucleus. With the development of chromosome conformation capture (1) and related techniques, researchers have begun to gain insight at the molecular level into how inter- and intrachromosome contacts are formed. Quantitative measurement of the contact frequencies in metazoans suggested the existence of topologically associating domains (TADs) as the building blocks of chromosome organization (1⇓–3). These domains are often demarcated by distinct patterns of histone modifications. For example, compartments that are enriched with H3K27me3 and have depleted H3K36me3 are signatures of facultative heterochromatin in the human genome. Although the features of chromosome organization have been characterized in several organisms, the principles and mechanisms governing the formation of chromosome organization have remained a mystery. In PNAS, Klocko et al. (4) report that the Polycomb Repressive Complex 2 (PRC2) and H3K27me3 have a role in shaping genome organization in Neurospora crassa. In mammalian and Drosophila cells, chromosomes are segregated into large TADs, and boundaries between adjacent TADs are characterized by enriched insulator protein CTCF occupancy (2, 3). Plants, yeast, and N. crassa lack large local interactive domains in their genomes, which is likely a result of the loss of genes encoding the CTCF protein (5, 6). The most obvious chromosomal contacts in plants and N. crassa genomes are formed between heterochromatin regions. However, H3K9me3 and the constitutive heterochromatin machinery seemed to be dispensable for this contact (5, 6). Fission yeast does not have H3K27 methylation, and its sole H3K9 methyltransferase is needed for proper genome organization (7). This result raises the question of whether H3K27 methylation and facultative heterochromatin contribute to genome structure formation. Klocko et al. (4) first profile chromosome organization with a high-throughput chromosome conformation capture (Hi-C) technique in …