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Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions

ABSTRACT: Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions

PROVIDER: PRJNA290789 | ENA |

REPOSITORIES: ENA

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Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions

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Project description:Histone post-translational modifications (PTM) encode much of genome's regulatory information. However, regular chromatin immunoprecipitation followed by sequencing (ChIP-seq) protocols trace histone PTM to genomic regions spanning several nucleosomes, making it difficult to study how different histone PTM combine within individual nucleosomes to regulate the genome. Here, we devised computational and statistical methods to map H3K4me3, H3K27Ac, H3K9me3, and H3K27me3 to individual nucleosomes using MNase digestion of chromatin coupled with ChIP-seq. A significant number of nucleosomes were marked by two or more of histone marks. Nucleosomes marked simultaneously by H3K4me3 and H3K27me3 were prevalent among bivalent domains compared to the genomic background whereas nucleosomes having the repressive marks H3K27me3 and H3K9me3 were enriched at the transcription staring site of highly active genes only if they were also co-localized with the activating mark H3K27Ac. Inclusion of alternatively spliced exons on the final mRNA is correlated with nucleosomes marked by H3K4me3, H3K27Ac, and H3K27me3, but is largely unaffected by nucleosomes marked by H3K9me3. Together, these findings reveal that combinatorial patterns of histone PTM within individual nucleosomes are fundamental to encode regulatory information.

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