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Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3 chromatin peaks.

Bell, CG; Wilson, GA; Beck, S; (2014) Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3 chromatin peaks. Epigenomics , 6 (1) 21 - 31. 10.2217/epi.13.74. Green open access

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Abstract

Background: Targeted recruitment of chromatin-modifying enzymes to clusters of CpG dinucleotides contributes toward the formation of accessible chromatin. By interprimate comparison we previously identified the set of nonpolymorphic human-specific CpGs (CpG 'beacons') and revealed that these loci were enriched for human disease traits. Due to their human-specific CpG density change, extreme CpG 'beacon' clusters (≥20 CpG beacons/kb) were predicted to identify permissive chromatin peaks within the human genome. Aim: We set out to explore these sequence-defined regions for evidence of an active chromatin signature. Results: Using available comparative primate epigenomic data from neurons of the prefrontal cortex, we show that these CpG 'beacon' clusters are indeed enriched for being human-specific H3K4me3 peaks (χ(2): p < 2.2 × 10(-16)) and thus predictive of permissive chromatin states. These sequence regions had a higher predictive value than previous selective analyses. We also show that both human-specific H3K4me3 and CpG 'beacon' clusters are increased within current and ancestral telomeric regions, supporting an association with recombination, which is higher towards the distal ends of chromosomes. Conclusion: Therefore, CpG-focused comparative sequence analysis can precisely pinpoint chromatin structures that contribute to the human-specific phenotype and further supports an integrated approach in genomic and epigenomic studies.

Type: Article
Title: Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3 chromatin peaks.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.2217/epi.13.74
Publisher version: http://dx.doi.org/10.2217/epi.13.74
Language: English
Additional information: This work is licensed under a Creative Commons, Attribution 3.0 (CC-BY) License
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1423623
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