http://orcid.org/0000-0003-4192-8983
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
DNA methylation (5-methylcytosine, 5 mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5 mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the “sixth base” of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain. Despite identifying over 17,000 high-confidence CpG sites with consistent 5hmC enrichment, the distribution of this modification in placenta is relatively sparse when compared to cerebellum and frontal cortex. Supported by validation using allelic T4 β-glucosyltransferase assays we identify 5hmC at numerous imprinted loci, often overlapping regions associated with parent-of-origin allelic 5 mC in both placenta and brain samples. Furthermore, we observe tissue-specific monoallelic enrichment of 5hmC overlapping large clusters of imprinted snoRNAs-miRNAs processed from long noncoding RNAs (lncRNAs) within the DLK1-DIO3 cluster on chromosome 14 and SNRPN-UBE3A domain on chromosome 15. Enrichment is observed solely on the transcribed alleles suggesting 5hmC is positively associated with transcription at these loci. Our study provides an extensive description of the 5hmC/5 mC landscape in placenta with our data available at www.humanimprints.net, which represents the most comprehensive resource for exploring the epigenetic profiles associated with human imprinted genes.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgements
We would like to thank all the families that participated in this study and the perinatal nurses at Hospital Sant Joan de Deú who contributed to the collection of placenta samples. This work was supported by Spanish Ministerio de Educación y Competitividad (MINECO) (BFU2014-53093 to DM) and the ISCIII (National Plan of R+D+I) (PI13/-1562 to IIP) co-funded with the European Union Regional Development Fund (FEDER). Brain samples were obtained from the Xarxa de Bancs de Tumors de Catalunya, which is sponsored by Pla Director d'Oncologia de Catalunya (XBTC).
