Gene‐body chromatin modification dynamics mediate epigenome differentiation in Arabidopsis

• Published in: The EMBO journal Vol. 36; no. 8; pp. 970 - 980
• Main Authors: Inagaki, Soichi, Takahashi, Mayumi, Hosaka, Aoi, Ito, Tasuku, Toyoda, Atsushi, Fujiyama, Asao, Tarutani, Yoshiaki, Kakutani, Tetsuji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.04.2017; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Arabidopsis - genetics; Arabidopsis - metabolism; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Chromatin; Defects; EMBO09; EMBO30; EMBO44; gene body; Gene expression; Gene Silencing; heterochromatin; Heterochromatin - metabolism; histone demethylase; histone methylation; Histones - genetics; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Methylation; Mutation; Protein Processing, Post-Translational; histone methylation; gene body; histone demethylase; heterochromatin
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201694983

Heterochromatin is marked by methylation of lysine 9 on histone H3 (H3K9me). A puzzling feature of H3K9me is that this modification localizes not only in promoters but also in internal regions (bodies) of silent transcription units. Despite its prevalence, the biological significance of gene‐body H3K9me remains enigmatic. Here we show that H3K9me‐associated removal of H3K4 monomethylation (H3K4me1) in gene bodies mediates transcriptional silencing. Mutations in an Arabidopsis H3K9 demethylase gene IBM1 induce ectopic H3K9me2 accumulation in gene bodies, with accompanying severe developmental defects. Through suppressor screening of the ibm1 ‐induced developmental defects, we identified the LDL2 gene, which encodes a homolog of conserved H3K4 demethylases. The ldl2 mutation suppressed the developmental defects, without suppressing the ibm1 ‐induced ectopic H3K9me2. The ectopic H3K9me2 mark directed removal of gene‐body H3K4me1 and caused transcriptional repression in an LDL2‐dependent manner. Furthermore, mutations of H3K9 methylases increased the level of H3K4me1 in the gene bodies of various transposable elements, and this H3K4me1 increase is a prerequisite for their transcriptional derepression. Our results uncover an unexpected role of gene‐body H3K9me2/H3K4me1 dynamics as a mediator of heterochromatin silencing and epigenome differentiation. Synopsis A genetic interaction between histone demethylases IBM1 and LDL2 reveals that H3K9 methylation in gene bodies induces transcriptional silencing by triggering the loss of H3K4 monomethylation. A mutation in putative H3K4 demethylase LDL2 suppresses the developmental defects seen in the Arabidopsis mutant of H3K9 demethylase IBM1. LDL2 functions downstream of ibm1 ‐induced ectopic H3K9 dimethylation in gene bodies to decrease H3K4me1 levels and repress gene expression. The gene‐body localized H3K9me2 mark represses expression of TEs via demethylation of H3K4me1. Counteracting demethylation of H3K9me2 and H3K4me1, together with transcription, can induce differentiation of active and inactive transcription units. Graphical Abstract A genetic interaction between histone demethylases IBM1 and LDL2 reveals that H3K9 methylation in gene bodies induces transcriptional silencing by triggering the loss of H3K4 monomethylation.