Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The S-adenosyl-homosteine hydrolase inhibitor DZNeP unspecifically affects histone methylation patterns in embryos and results in developmental aberrations

ABSTRACT: 3-deazaneplanocin A (DZNeP) is a promising cancer drug affecting the methylation status of histone lysine residues. To investigate the specificity and mode of action of DZNeP, zebrafish embryos displaying high histone methyltransferase activity were cultured with DZNeP and histone methylation (H3K4me3, H3K9me3, H3K27me3) was mapped by ChIP-chip genome-wide promoter at post-MBT stage (5.3 hpf) . We used a custom 2.1M probe HD promoter array (Nimblegen) for ChIP and input DNA hybridization. Peak detection was done using MA2C with P=10e-4 as cutoff. ChIP-chip experiments were performed from chromatin prepared by sonication after formaldehyde cross-linking, from embryos are the indicated developmental stages and ChIP DNA was hybridized onto the aforementioned Nimbegen promoter arrays.

ORGANISM(S): Danio rerio

SUBMITTER: Philippe Collas

PROVIDER: E-GEOD-53209 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The specific alteration of histone methylation profiles by DZNep during early zebrafish development.

Ostrup Olga O Reiner Andrew H AH Aleström Peter P Collas Philippe P

Biochimica et biophysica acta 20140928 11

Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embryos were cultured with DZNep, and subsequently evaluated at the post-mid blastula transition stage for H3K27me3, H3K4me3 and H3K9me3 occupancy and enrichment at promoters using ChIP-c ...[more]

PMID: 25260724

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Project description:Epigenetic environment of histone H3.3 on promoters revealed by integration of imaging and genome-scale chromatin and methyl-DNA immunoprecipitation information. Chromatin regions with different transcriptional outputs are distinguished by the deposition of histone variants. Histone H3.3 is incorporated into chromatin in a replication-independent manner; yet the relationship between H3.3 deposition, chromatin environment is incompletely understood. We have integrated imaging and genome-scale chromatin and methyl-DNA immunoprecipitation approaches to investigate the genomic distribution of epitope-tagged H3.3 in relation to histone modifications, DNA methylation and transcription. Results: Imaging shows that H3.3, in contrast to replicative H3.1 or H2B, is enriched in chromatin marked by histone modifications of active genes. A genome-wide survey identifies 1,649 H3.3-enriched promoters, only a subset of which is co-enriched in H3K4me3, H3K9me3 and/or H3K27me3, with a preference for H3K4me3, corroborating imaging data. H3.3-enriched promoters are depleted of H3.3 at the TSS in a transcription-independent manner. H3.3 is found predominantly on CpG-rich unmethylated promoters, creating a condition favourable for transcription. In undifferentiated mesenchymal stem cells, H3.3 target genes are linked to signaling and mesodermal differentiation, suggesting that H3.3 may be a mark of lineage priming. Conclusions: A minor fraction of H3.3 is targeted to promoters, which are predominantly CpG-rich, DNA unmethylated and devoid of detectable trimethylated H3K4, K9 and K27. Among H3.3 target promoters co-marked by methylated H3, H4K4me3 is preferred, with or without H3K27me3, arguing that in mesenchymal stem cells H3.3 marks transcriptionally active or potentially active promoters. Key words: Imaging, ChIP-chip, MeDIP-chip, histone H3.3, mesenchymal stem cells ChIP-chip and MeDIP-chip experiments: Performed with two independent biological replicates. Gene expression profiling experiments: Total RNA obtained from H3.3-EGFP transfected or empty-EGFP transfected mesenchymal stem cells compared to untransfected mesenchymal stem cells. Raw expression data linked below as supplementary file (GSE17053_Illumina_non-normalized_data.txt).

Dataset Information

The S-adenosyl-homosteine hydrolase inhibitor DZNeP unspecifically affects histone methylation patterns in embryos and results in developmental aberrations

Publications

The specific alteration of histone methylation profiles by DZNep during early zebrafish development.

Similar Datasets

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