Dataset Information

Genome-wide Analysis of Mono-, Di- and Trimethylation of Histone H3 Lysine 4 in Arabidopsis thaliana

ABSTRACT: Background. Post-translational modifications of histones play important roles in regulating transcription by modulating the structural properties of the chromatin. In plants, methylation of histone H3 lysine4 (H3K4me) is associated with genes and required for normal plant development. Results. We have characterized the genome-wide distribution patterns of mono-, di- and trimethylation of H3K4 (H3K4me1, H3K4me2 and H3K4me3, respectively) in Arabidopsis thaliana using chromatin immunoprecipitation and high-resolution whole-genome tiling microarrays (ChIP-chip). All three types of H3K4me are found to be almost exclusively genic, and two thirds of Arabidopsis genes contain at least one type of H3K4me in seedlings. H3K4me2 and H3K4me3 accumulate predominantly in promoters and 5’ genic regions, whereas H3K4me1 is distributed within transcribed regions. In addition, H3K4me3-containing genes are highly expressed with low levels of tissue specificity, but H3K4me1 or H3K4me2 may not be directly involved in transcriptional activation. Furthermore, a genome-wide preferential co-localization of H3K4me3 and H3K27me3 found in mammals does not appear to exist in plants, but H3K4me2 and H3K27me3 co-localize at a higher-than-expected frequency. Finally, the relationship between H3K4me and DNA methylation was explored by comparing the genome-wide distribution patterns of H3K4me1, H3K4me2 and H3K4me3 in wild type plants and the met1 DNA methyltransferase mutant. Conclusions. H3K4me plays widespread roles in regulating gene expression in plants. Although many aspects of the mechanisms and functions of H3K4me appear to be conserved among all three kingdoms, we observed significant differences in the relationship between H3K4me and transcription or other epigenetic pathways in plants and mammals.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE13613 | GEO | 2009/02/01

SECONDARY ACCESSION(S): PRJNA110635

REPOSITORIES: GEO

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Project description:FOXA1 is a pioneer factor that is important in hormone dependent cancer cells to stabilise nuclear receptors, such as estrogen receptor (ER) to chromatin. FOXA1 binds to enhancers regions that are enriched in H3K4mono- and dimethylation (H3K4me1, H3K4me2) histone marks and evidence suggests that these marks are requisite events for FOXA1 to associate with enhancers to initate subsequent gene expression events. However, exogenous expression of FOXA1 has been shown to induce H3K4me1 and H3K4me2 signal at enhancer elements and the order of events and the functional importance of these events is not clear. We performed a FOXA1 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells in order to identify FOXA1 interacting partners and we found histone-lysine N-methyltransferase (MLL3) as the top FOXA1 interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition, in line with our observation that MLL3 associates with an enhancer specific protein. We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.

Dataset Information

Genome-wide Analysis of Mono-, Di- and Trimethylation of Histone H3 Lysine 4 in Arabidopsis thaliana

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