Epigenetic factors direct synergistic and antagonistic regulation of transposable elements in Arabidopsis

Arabidopsis (Arabidopsis thaliana) HISTONE DEACETYLASE 6 (HDA6) and HISTONE DEMETHYLASES LSD-LIKE 1 (LDL1) and LDL2 synergistically regulate the expression of long non-coding RNAs associated with H3Ac and H3K4me2. The underlying mechanisms of such highly coordinated interactions among genetic and epigenetic factors contributing to this collaborative regulation remain largely unclear. We analyzed all transposable elements (TEs) across the Arabidopsis genome and the individual and combined roles of HDA6 and LDL1/LDL2 by dissecting multilayered epigenomes and their association with transcription. Instead of an individual synergistic effect, we observed dual synergistic and antagonistic effects, which are positively associated with H3Ac and H3K4me2 while maintaining a negative but moderate association with DNA methylation. Specifically, 2 modes of synergistic regulation were discovered in TEs: 74% are primarily regulated by HDA6, with less dependence on LDL1/LDL2, and the remaining 26% are co-regulated by both. Between the 2 modes, we showed that HDA6 has a strong effect on TE silencing, whereas LDL1/LDL2 plays a weaker yet crucial role in co-regulation with HDA6. Our results led to a model of epigenomic regulation-the differential de-repression between the 2 modes of synergistic regulation of TEs was determined by H3Ac and H3K4me2 levels, where TEs are in accessible chromatins free of DNA methylation, and this open chromatin environment precedes transcriptional changes and epigenome patterning. Our results discovered unbalanced effects of genetic factors in synergistic regulation through delicately coordinated multilayered epigenomes and chromatin accessibility.