Dataset Information

Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation.

ABSTRACT: Mono-, di-, and trimethylation of histone H3 lysine 4 (H3K4me1/2/3) are associated with transcription, yet it remains controversial whether H3K4me1/2/3 promote or result from transcription. Our previous characterizations of Arabidopsis H3K4 demethylases suggest roles for H3K4me1 in transcription. However, the control of H3K4me1 remains unexplored in Arabidopsis, in which no methyltransferase for H3K4me1 has been identified. Here, we identify three Arabidopsis methyltransferases that direct H3K4me1. Analyses of their genome-wide localization using ChIP-seq and machine learning reveal that one of the enzymes cooperates with the transcription machinery, while the other two are associated with specific histone modifications and DNA sequences. Importantly, these two types of localization patterns are also found for the other H3K4 methyltransferases in Arabidopsis and mice. These results suggest that H3K4me1/2/3 are established and maintained via interplay with transcription as well as inputs from other chromatin features, presumably enabling elaborate gene control.

SUBMITTER: Oya S

PROVIDER: S-EPMC9372134 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation.

Oya Satoyo S Takahashi Mayumi M Takashima Kazuya K Kakutani Tetsuji T Inagaki Soichi S

Nature communications 20220811 1

Mono-, di-, and trimethylation of histone H3 lysine 4 (H3K4me1/2/3) are associated with transcription, yet it remains controversial whether H3K4me1/2/3 promote or result from transcription. Our previous characterizations of Arabidopsis H3K4 demethylases suggest roles for H3K4me1 in transcription. However, the control of H3K4me1 remains unexplored in Arabidopsis, in which no methyltransferase for H3K4me1 has been identified. Here, we identify three Arabidopsis methyltransferases that direct H3K4m ...[more]

PMID: 35953471

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Project description:Epigenetic regulation of gene expression has been shown to change over time and may be associated with environmental exposures in common complex traits. Age-related hearing impairment is a complex disorder, known to be heritable, with heritability estimates of 57-70%. Epigenetic regulation might explain the observed difference in age of onset and magnitude of hearing impairment with age. Epigenetic epidemiology studies using unrelated samples can be limited in their ability to detect small effects, and recent epigenetic findings in twins underscore the power of this well matched study design. We investigated the association between venous blood DNA methylation epigenome-wide and hearing ability. Pure-tone audiometry (PTA) and Illumina HumanMethylation array data were obtained from female twin volunteers enrolled in the TwinsUK register. Two study groups were explored: first, an epigenome-wide association scan (EWAS) was performed in a discovery sample (n=115 subjects, age range: 47-83 years, Illumina 27 k array), then replication of the top ten associated probes from the discovery EWAS was attempted in a second unrelated sample (n=203, age range: 41-86 years, Illumina 450 k array). Finally, a set of monozygotic (MZ) twin pairs (n = 21 pairs) within the discovery sample (Illumina 27 k array) was investigated in more detail in an MZ discordance analysis. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25 (cg01161216, p = 6.6 × 10(-6)), FGFR1 (cg15791248, p = 5.7 × 10(-5) and POLE (cg18877514, p= 6.3 × 10(-5)). Replication of these results in a second sample confirmed the presence of differential methylation at TCF25 (p(replication)=6 × 10(-5)) and POLE (p(replication) =0.016). In the MZ discordance analysis, twins' intrapair difference in hearing ability correlated with DNA methylation differences at ACP6 (cg01377755, r= -0.75, p=1.2 × 10(-4)) and MEF2D (cg08156349, r= -0.75, p=1.4 × 10(-4)). Examination of gene expression in skin, suggests an influence of differential methylation on expression, which may account for the variation in hearing ability with age.

Dataset Information

Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation.

Publications

Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation.

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