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| Status |
Public on Sep 01, 2015 |
| Title |
5-hydroxymethylcytosine is linked with expression of brain-specific protein-coding genes but not brain-specific microRNA host genes [hMeDIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation (5mC) is an epigenetic modification classified by the addition of a methyl group (Ch3-) catalysed by DNA methyltransferases (DNMTs) and S-adenosyl methionine (SAM). Recently hydroxymethylation at the same carbon-5 residue of the cytosine base catalysed by the TET (Ten–Eleven Translocation) family of proteins has been shown occur in mouse embryonic stem cells and the brain. 5-hydroxymethylcytosine (5hmC) has been shown to be distributed at a lesser extent in most mammalian tissues with an increased occurrence in Purkinje cells of the mouse brain. Here we assess genome-wide 5hmC distribution relative to 5mC enrichment in the human cerebellum and peripheral blood lymphocytes (PBLs) using high-resolution sequencing by synthesis. We found a significant increase and change in 5hmC distribution in human cerebellum at loci highly expressed in the human brain and postsynaptic density (PSD) compared to PBLs. Minimal changes in 5mC distribution were observed at these same loci and genome-wide in both human cerebellum and PBLs. Using high-throughput RNA-Seq of total RNA from human brain, cerebellum and PBLs we quantified elevated expression of gene products implicated in neuronal activity and having significantly increased 5hmC distribution across their gene bodies only in brain tissue compared to PBLs. Furthermore we show elevated expression of gene loci in the cerebellum to co-localise with increased 5hmC in Purkinje neurons. Our data provide new evidence for 5hmC mediated regulation of gene loci highly expressed in the human brain and PSD and implicated in neuronal activity and development.
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| Overall design |
Examination of hydroxymethylation (hMeDIP-Seq), hypermethylation (MBD-Seq using a his-MBD2B antibody) and hypomethylation (MRE-Seq using HpaII restriction enzyme digestion) in genomic DNA from human cerebellum and peripheral blood lymphocytes
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| Contributor(s) |
Minocherhomji S, Mang Y, Tommerup N, Silahtaroglu A |
| Citation missing |
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| Submission date |
Dec 21, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Sheroy Minocherhomji |
| E-mail(s) |
sheroy@sund.ku.dk
|
| Organization name |
University of Copenhagen
|
| Department |
Nordea Centre for Healthy Aging, Faculty Of Health Sciences Department of Cellular and Molecular Medicine
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| Lab |
Ian D. Hickson lab
|
| Street address |
Blegdamsvej 3B, Building 18.1
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| City |
Copenhagen |
| State/province |
Copenhagen N |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE35238 |
5-hydroxymethylcytosine is linked with expression of brain-specific protein-coding genes but not brain-specific microRNA host genes |
|
| Relations |
| SRA |
SRP009913 |
| BioProject |
PRJNA156197 |
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