Local and global crosstalk among heterochromatin marks drives epigenome patterning in Arabidopsis

Transposable elements (TEs) are robustly silenced by targeting of multiple epigenetic marks, but dynamics of crosstalk among these marks remains enigmatic. In Arabidopsis, TEs are silenced by cytosine methylation in both CpG and non-CpG contexts (mCG and mCH) and histone H3 lysine 9 methylation (H3K9me). While mCH and H3K9me are mutually dependent for their maintenance, mCG and mCH/H3K9me are independently maintained. Here we show that establishment, rather than maintenance, of mCH depends on mCG, accounting for the synergistic colocalization of these silent marks in TEs. When mCG is lost, establishment of mCH is abolished in TEs. mCG also guides mCH in active genes, although genic mCH/H3K9me is removed there. Unexpectedly, the targeting efficiency of mCH depends on relative, rather than absolute, levels of mCG, suggesting underlying global negative controls. We propose that the local positive feedback in heterochromatin dynamics, together with global negative feedback, drive robust and balanced epigenome patterning.