DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes chromatin modification patterns

Abstract

The stability of epigenetic patterns is critical for genome integrity and gene expression. This highly coordinated process involves interrelated positive and negative regulators that impact distinct epigenetic marks, including DNA methylation and dimethylation at histone H3 lysine 9 (H3K9me2). In Arabidopsis, mutations in the DNA methyltransferase MET1, which maintains CG methylation, result in aberrant patterns of other epigenetic marks, including ectopic non-CG methylation and the relocation of H3K9me2 from heterochromatin into generich chromosome regions. Here, we show that the expression of the H3K9 demethylase IBM1 (increase in BONSAI methylation 1) requires DNA methylation. Surprisingly, the regulatory methylated region is contained in an unusually large intron that is conserved in IBM1 orthologues. The re-establishment of IBM1 expression in met1 mutants restored the wild-type H3K9me2 nuclear patterns, non-CG DNA methylation and transcriptional patterns at selected loci, which included DNA demethylase genes. These results provide a mechanistic explanation for long-standing puzzling observations in met1 mutants and reveal yet another layer of control in the interplay between DNA methylation and histone modification, which stabilizes DNA methylation patterns at genes.

Mechanism for full-length RNA processing of Arabidopsis genes containing intragenic heterochromatin

“…1c, Supplementary Fig. S8a,b) 14,20 . As the reduction of IBM1 transcripts in ibm2 occurred specifically at the 3 0 region downstream of the intron containing the heterochromatic domain, we speculated that fulllength transcription of IBM1 might be hindered by this sequence.…”

“…Therefore, it is possible that IBM2 prevents premature transcriptional termination by suppressing antisense transcription from cryptic promoters. Indeed, the production of antisense transcripts was detected from the heterochromatic domain of the IBM1 locus 20 . Alternatively, binding of the RRM domain to pre-mRNA might directly suppress utilization of alternative poly(A) signals near or within heterochromatic domain, which would eventually promote splicing of the intron containing heterochromatin 38 .…”

“…It has been demonstrated that full-length IBM1 mRNA is reduced in the met1 mutant, due to a loss of DNA methylation at the heterochromatinc domain 20,40 . Because IBM1 encodes a histone H3K9 demethylase 19 , the heterochromatic domain in IBM1 may function as a genomewide fine-tuning mechanism, balancing active and repressive states of genes and TEs, through the control of full-length transcription of IBM1 20 .…”

Epigenome confrontation triggers immediate reprogramming of DNA methylation and transposon silencing inArabidopsis thalianaF1 epihybrids

“…sites. Lack of either type of methylation in this region disrupts the heterochromatin structure and is associated with impaired production of the long IBM1 transcript IBM1-L, which encodes the functional form of IBM1 (23,25). In addition to the ROS1-and IBM1-mediated defects in met1 mutants, genes premarked with H3K27me3 tend to gain ectopic H3K9me2 and to be depleted in H3K27me3 in met1 whereas heterochromatic loci show depletion in H3K9me2 and ectopic H3K27me3 upon CG methylation loss (26,27).…”

Osteogenic Gene Transcription Is Regulated via Gap Junction-Mediated Cell–Cell Communication

“…Based on these reports, miRNAs may be likely candidates for the role of molecular messengers between MLO-A5 and 10T-GFP cells, although this hypothesis requires experimental validation. Methylation of genomic DNA is an essential mechanism by which gene transcription is regulated in eukaryotes [34][35][36][37]. In addition, acetylation of the core histones that make up the nucleosome (such as H2A, H2B, H3, and H4) causes chromatin remodeling and promotes gene transcription [38][39][40].…”