Caenorhabditis elegans Deficient in DOT-1.1 Exhibit Increases in H3K9me2 at Enhancer and Certain RNAi-Regulated Regions

Abstract

The methylation of histone H3 at lysine 79 is a feature of open chromatin. It is deposited by the conserved histone methyltransferase DOT1. Recently, DOT1 localization and H3K79 methylation (H3K79me) have been correlated with enhancers in <i>C. elegans</i> and mammalian cells. Since earlier research implicated H3K79me in preventing heterochromatin formation both in yeast and leukemic cells, we sought to inquire whether a H3K79me deficiency would lead to higher levels of heterochromatic histone modifications, specifically H3K9me2, at developmental enhancers in <i>C. elegans.</i> Therefore, we used H3K9me2 ChIP-seq to compare its abundance in control and <i>dot-1.1</i> loss-of-function mutant worms, as well as in <i>rde-4; dot-1.1</i> and <i>rde-1; dot-1.1</i> double mutants. The <i>rde-1</i> and <i>rde-4</i> genes are components of the RNAi pathway in <i>C. elegans</i>, and RNAi is known to initiate H3K9 methylation in many organisms, including <i>C. elegans</i>. We have previously shown that <i>dot-1.1(-)</i> lethality is rescued by <i>rde-1</i> and <i>rde-4</i> loss-of-function. Here we found that H3K9me2 was elevated in enhancer, but not promoter, regions bound by the DOT-1.1/ZFP-1 complex in <i>dot-1.1(-)</i> worms. We also found increased H3K9me2 at genes targeted by the ALG-3/4-dependent small RNAs and repeat regions. Our results suggest that ectopic H3K9me2 in <i>dot-1.1(-)</i> could, in some cases, be induced by small RNAs.