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dc.contributor.authorLee, Bernetten_US
dc.contributor.authorCyrill, Samantha Leeanneen_US
dc.contributor.authorLee, Wendyen_US
dc.contributor.authorMelchiotti, Rossellaen_US
dc.contributor.authorAndiappan, Anand Kumaren_US
dc.contributor.authorPoidinger, Michaelen_US
dc.contributor.authorRötzschke, Olafen_US
dc.identifier.citationLee, B., Cyrill, S. L., Lee, W., Melchiotti, R., Andiappan, A. K., Poidinger, M. & Rötzschke, O. (2022). Analysis of archaic human haplotypes suggests that 5hmC acts as an epigenetic guide for NCO recombination. BMC Biology, 20(1).
dc.description.abstractBackground: Non-crossover (NCO) refers to a mechanism of homologous recombination in which short tracks of DNA are copied between homologue chromatids. The allelic changes are typically restricted to one or few SNPs, which potentially allow for the gradual adaptation and maturation of haplotypes. It is assumed to be a stochastic process but the analysis of archaic and modern human haplotypes revealed a striking variability in local NCO recombination rates. Methods: NCO recombination rates of 1.9 million archaic SNPs shared with Denisovan hominids were defined by a linkage study and correlated with functional and genomic annotations as well as ChIP-Seq data from modern humans. Results: We detected a strong correlation between NCO recombination rates and the function of the respective region: low NCO rates were evident in introns and quiescent intergenic regions but high rates in splice sites, exons, 5′- and 3′-UTRs, as well as CpG islands. Correlations with ChIP-Seq data from ENCODE and other public sources further identified epigenetic modifications that associated directly with these recombination events. A particularly strong association was observed for 5-hydroxymethylcytosine marks (5hmC), which were enriched in virtually all of the functional regions associated with elevated NCO rates, including CpG islands and ‘poised’ bivalent regions. Conclusion: Our results suggest that 5hmC marks may guide the NCO machinery specifically towards functionally relevant regions and, as an intermediate of oxidative demethylation, may open a pathway for environmental influence by specifically targeting recently opened gene loci.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.relation.ispartofBMC Biologyen_US
dc.rights© The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver (http://creativeco applies to the data made available in this article, unless otherwise stated in a credit line to the data.en_US
dc.titleAnalysis of archaic human haplotypes suggests that 5hmC acts as an epigenetic guide for NCO recombinationen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.organizationSingapore Immunology Network (SIgN) (A*STAR).en_US
dc.description.versionPublished versionen_US
dc.subject.keywordsMeiotic Recombinationen_US
dc.subject.keywordsEpigenetic Inheritanceen_US
dc.description.acknowledgementAll the Singapore Immunology Network authors are supported by the A*STAR/Singapore Immunology Network core grant.en_US
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