Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Epigenetic regulation of gene expression is instructed by promoter sequence and refined by developmental progression [expression]

ABSTRACT: A large body of literature suggests that local features of chromatin are crucial in determining functional properties of underlying DNA. The extent to which DNA sequence plays an active role in the establishment and maintenance of patterns of histone and DNA modification at promoters in cells and tissues in an adult animal remains poorly understood. Likewise, whether passage through development is required for refinement of transcriptional states and chromatin marks characteristic of fully differentiated adult cells remains unclear. Here we undertook analysis of gene expression along with the genomic distribution of DNA methylation and a set of histone marks in primary tissues derived from different primordial germ layers in adult mice. We find that promoter CpG content correlated strongly with specific repressive mechanisms. Likewise, RNA polymerase II occupancy and active histone marks were omnipresent on CpG rich promoters regardless of transcriptional output and of cell type. However, these same chromatin features cleanly demarcate transcriptional activity on promoters with low CpG content. While these observations imply an instructive role for DNA sequence in establishment and maintenance of epigenetic states, experimental evidence presented here also suggests an additional role for development in refining these features at individual promoters. Gene expression in B cells and liver was measured using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Deepak Mav

PROVIDER: E-GEOD-41449 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

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

Epigenetic regulation of gene expression is instructed by promoter sequence and refined by developmental progression [expression]

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets