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CpG islands under selective pressure are enriched with H3K4me3, H3K27ac and H3K36me3 histone modifications.

ABSTRACT: BACKGROUND: Histone modification is an epigenetic mechanism that influences gene regulation in eukaryotes. In particular, histone modifications in CpG islands (CGIs) are associated with different chromatin states and with transcription activity. Changes in gene expression play a crucial role in adaptation and evolution. RESULTS: In this paper, we have studied, using a computational biology approach, the relationship between histone modifications in CGIs and selective pressure in Homo sapiens. We considered three histone modifications: histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 27 acetylation (H3K27ac) and histone H3 lysine 36 trimethylation (H3K36me3), and we used the publicly available genomic-scale histone modification data of thirteen human cell lines. To define regions under selective pressure, we used three distinct signatures that mark selective events from different evolutionary periods. We found that CGIs under selective pressure showed significant enrichments for histone modifications. CONCLUSION: Our result suggests that, CGIs that have undergone selective events are characterized by epigenetic signatures, in particular, histone modifications that are distinct from CGIs with no evidence of selection.

SUBMITTER: Akhtar MM

PROVIDER: S-EPMC3711888 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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CpG islands under selective pressure are enriched with H3K4me3, H3K27ac and H3K36me3 histone modifications.

Akhtar Most Mauluda MM Scala Giovanni G Cocozza Sergio S Miele Gennaro G Monticelli Antonella A

BMC evolutionary biology 20130710

<h4>Background</h4>Histone modification is an epigenetic mechanism that influences gene regulation in eukaryotes. In particular, histone modifications in CpG islands (CGIs) are associated with different chromatin states and with transcription activity. Changes in gene expression play a crucial role in adaptation and evolution.<h4>Results</h4>In this paper, we have studied, using a computational biology approach, the relationship between histone modifications in CGIs and selective pressure in Hom ...[more]

PMID: 23837650

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Project description:BackgroundThe development and application of CRISPR technologies for the modification of the genome are rapidly expanding. Advances in the field describe new CRISPR components that are strategically engineered to improve the precision and reliability of CRISPR editing within the genome sequence. Genome modification using induced genome breaks that are targeted and mediated by CRISPR components leverage cellular mechanisms for repair like homology directed repair (HDR) to incorporate genomic edits with increased precision.ResultsIn this report, we describe the gain of methylation at typically hypomethylated CpG island (CGI) locations affected by the CRISPR-mediated incorporation of donor DNA using HDR mechanisms. With characterization of CpG methylation patterns using whole genome bisulfite sequencing, these CGI methylation disruptions trace the insertion of the donor DNA during the genomic edit. These insertions mediated by homology-directed recombination disrupt the generational methylation pattern stability of the edited CGI within the cells and their cellular lineage within the animal strain, persisting across generations. Our approach describes a statistically based workflow for indicating locations of modified CGIs and provides a mechanism for evaluating the directed modification of the methylome of the affected CGI at the CpG-level.ConclusionsWith advances in genome modification technology comes the need to detect the level and persistence of methylation change that modifications to the genomic sequence impose upon the collaterally edited methylome. Any modification of the methylome of somatic or germline cells could have implications for gene regulation mechanisms governed by the methylation patterns of CGI regions in the application of therapeutic edits of more sensitively regulated genomic regions. The method described here locates the directed modification of the mouse epigenome that persists over generations. While this observance would require supporting molecular observations such as direct sequence changes or gene expression changes, the observation of epigenetic modification provides an indicator that intentionally directed genomic edits can lead to collateral, unintentional epigenomic changes post modification with generational persistence.

Dataset Information

CpG islands under selective pressure are enriched with H3K4me3, H3K27ac and H3K36me3 histone modifications.

Publications

CpG islands under selective pressure are enriched with H3K4me3, H3K27ac and H3K36me3 histone modifications.

Similar Datasets

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