PMID- 28989734 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210109 IS - 2054-5703 (Print) IS - 2054-5703 (Electronic) IS - 2054-5703 (Linking) VI - 4 IP - 9 DP - 2017 Sep TI - Detecting rare asymmetrically methylated cytosines and decoding methylation patterns in the honeybee genome. PG - 170248 LID - 10.1098/rsos.170248 [doi] LID - 170248 AB - Context-dependent gene expression in eukaryotes is controlled by several mechanisms including cytosine methylation that primarily occurs in the CG dinucleotides (CpGs). However, less frequent non-CpG asymmetric methylation has been found in various cell types, such as mammalian neurons, and recent results suggest that these sites can repress transcription independently of CpG contexts. In addition, an emerging view is that CpG hemimethylation may arise not only from deregulation of cellular processes but also be a standard feature of the methylome. Here, we have applied a novel approach to examine whether asymmetric CpG methylation is present in a sparsely methylated genome of the honeybee, a social insect with a high level of epigenetically driven phenotypic plasticity. By combining strand-specific ultra-deep amplicon sequencing of illustrator genes with whole-genome methylomics and bioinformatics, we show that rare asymmetrically methylated CpGs can be unambiguously detected in the honeybee genome. Additionally, we confirm differential methylation between two phenotypically and reproductively distinct castes, queens and workers, and offer new insight into the heterogeneity of brain methylation patterns. In particular, we challenge the assumption that symmetrical methylation levels reflect symmetry in the underlying methylation patterns and conclude that hemimethylation may occur more frequently than indicated by methylation levels. Finally, we question the validity of a prior study in which most of cytosine methylation in this species was reported to be asymmetric. FAU - Welsh, Laura AU - Welsh L AD - Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia. FAU - Maleszka, Ryszard AU - Maleszka R AUID- ORCID: 0000-0003-1855-555X AD - Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia. FAU - Foret, Sylvain AU - Foret S AD - Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia. LA - eng SI - figshare/10.6084/m9.figshare.c.3861829 SI - Dryad/10.5061/dryad.7nb8q PT - Journal Article DEP - 20170906 PL - England TA - R Soc Open Sci JT - Royal Society open science JID - 101647528 PMC - PMC5627074 OTO - NOTNLM OT - DNA methylation OT - epigenomics OT - social insect COIS- We have no competing interests. EDAT- 2017/10/11 06:00 MHDA- 2017/10/11 06:01 PMCR- 2017/09/06 CRDT- 2017/10/10 06:00 PHST- 2017/03/15 00:00 [received] PHST- 2017/08/07 00:00 [accepted] PHST- 2017/10/10 06:00 [entrez] PHST- 2017/10/11 06:00 [pubmed] PHST- 2017/10/11 06:01 [medline] PHST- 2017/09/06 00:00 [pmc-release] AID - rsos170248 [pii] AID - 10.1098/rsos.170248 [doi] PST - epublish SO - R Soc Open Sci. 2017 Sep 6;4(9):170248. doi: 10.1098/rsos.170248. eCollection 2017 Sep.