Identification of methylation and hydroxymethylation haplotype blocks as distal regulatory elements aids in deconvolution of heterogeneous brain tissues
5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in the mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC, respectively, at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently had 5mC modification simultaneously and enriched in gene body regions of neuron development related genes in brain tissues. These results supported a prominent role of oxidizing 5mC to 5hmC as new epigenetic mark. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation(MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions which further supported that oxidized 5mC to 5hmC co-ordinately in a subset of cells within heterogeneous brain tissues. Consistently, using a metric called methylation haplotype load, we defined a subset of 1,361 tissue-specific MHBs and 3,818 shared MHBs which were predominantly regulatory elements, and aids in deconvolution of heterogeneous brain tissues. Our results provide new insights into the role of co-ordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.
- Downloaded 699 times
- Download rankings, all-time:
- Site-wide: 37,842
- In genetics: 1,751
- Year to date:
- Site-wide: 96,000
- Since beginning of last month:
- Site-wide: 62,103
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!