Microrchidia ATPases and DNA 6mA demethylase ALKBH1 act antagonistically on PRC2 to control chromatin structure and stress tolerance

The Microrchidia (MORC) proteins are conserved GHKL-type ATPases required for chromatin condensation and gene silencing in animals and plants. Here we show that MORC proteins function with Polycomb-Repressive Complex 2 (PRC2) to control chromatin structure, gene expression and stress responses in rice. Rice MORC6b interacts with and stabilizes PRC2 for trimethylated histone H3 lysine 27 (H3K27me3) deposition preferentially at bivalent domains marked by both H3K4me3 and H3K27me3 to repress genes enriched for stress responses. The MORC-binding sites perfectly overlap with a set of PRC2 targets and colocalize with chromatin loop boundaries. High-throughput chromatin conformation capture combined with chromatin immunoprecipitation (Hi-ChIP) analysis revealed that the morc mutation reduces the number of H3K27me3-marked chromatin loops mainly at bivalent domains compressing many defence-related genes and affects rice plant tolerance to biotic and abiotic stresses. MORC function in H3 K27 trimethylation and gene expression is partly inhibited by ALKBH1, a DNA 6mA demethylase that impairs PRC2 binding and H3K27me3 deposition at bivalent chromatin domains and has an opposite function to MORC in stress responses. These findings identify MORCs and ALKBH1 as an antagonistic couple controlling PRC2 function in regulating chromatin structure and gene expression preferentially at bivalent chromatin domains for stress responses, which is instructive for understanding the regulation of chromatin dynamics in other eukaryotic organisms. In this work, Zhang, Jia, Wang et al. show that MORCs stabilize PRC2 preferentially at bivalent domains to maintain high levels of H3 K27 trimethylation and form chromatin loops for gene repression and stress tolerance, and are counteracted by ALKBH1, a DNA 6mA demethylase.