Figure 11.

Control of X-chromosome histone modification, topology, and repression by a histone H4K20 demethylase DCC subunit that catalyzes formation of H4K20me1. (A) During the establishment and maintenance of dosage compensation, the DCC enriches the histone modification H4K20me1 on both hermaphrodite X chromosomes. H4K20me1 is also enriched on the inactive X chromosome of female mammals, revealing a common feature of diverse dosage compensation strategies. (B) The DPY-21 H4K20me2 histone demethylase regulates 3D X-chromosome structure and gene expression by catalyzing enrichment of H4K20me1. The 1.8 Å crystal structure of DPY-21 and biochemical assays in vitro identified a novel, highly conserved H4K20me2 JmjC demethylase subfamily that converts H4K20me2 to H4K20me1 in an Fe²⁺ and α-ketoglutarate-dependent manner. In somatic cells, DPY-21 binds to X chromosomes via the DCC and enriches H4K20me1 to repress gene expression. The H4K20me1 enrichment controls the higher-order structure of X chromosomes by facilitating compaction and TAD formation. In germ cells, DPY-21 enriches HK20me1 on autosomes, but not X, in a DCC-independent manner to promote chromosome compaction.