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Series GSE77447 Query DataSets for GSE77447
Status Public on May 31, 2016
Title In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine
Organism Mus musculus
Experiment type Other
Summary Background: Genome-wide methylation of cytosine can be modulated in the presence of TET and thymine DNA glycosylase (TDG) enzymes. TET enzymes are able to oxidise 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TDG can excise the oxidative products 5fC and 5caC, initiating base excision repair. Furthermore, these modified bases are stable and detectable in the genome, raising the possibility that they could have epigenetic functions in their own right. To date, functional investigation of the genome-wide distribution of 5fC has been restricted to cell culture based systems, while its in vivo profile, in particular during development, remains unknown.
Results: Here we describe the first analysis of the in vivo genome-wide profile of 5fC, across a range of dissected tissues from both wild type and Tdg-deficient E11.5 mouse embryos. Changes in the formylation profile of cytosine upon depletion of TDG suggest TET/TDG-mediated active demethylation occurs preferentially at intron-exon boundaries, and reveals a major role for TDG in shaping 5fC distribution at CpG islands. Moreover, we find enhancer regions exhibit high levels of 5fC, which accumulates at tissue-specific enhancers implicating a role in embryonic development.
Conclusions: The tissue-specific distribution of 5fC can be regulated by the collective contribution of TET-mediated oxidation and excision by TDG. We show that the in vivo profile of 5fC during embryonic development resembles that of embryonic stem cells, sharing key features including enrichment of 5fC in enhancer and intragenic regions. Additionally, by investigating 5fC profiles in a tissue-specific manner from mouse embryos, we identified a targeted enrichment at active enhancers involved in tissue development.
Overall design 5-formylcytosine has been mapped genomewide by pull-down and sequencing in mouse hindbrain, heart, carcass and liver. Each tissue was replicated in two different mice except for hindbrain which was replicated in four different mice.
Contributor(s) Iurlaro M, McInroy GR, Burgess HE, Dean W, Raiber E, Bachman M, Beraldi D, Balasubramanian S, Reik W
Citation(s) 27356509
Submission date Feb 01, 2016
Last update date May 15, 2019
Contact name Dario Beraldi
Organization name Cambridge Research Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (20)
GSM2051990 brain_KO_2A2
GSM2051992 brain_KO_O4
GSM2051994 brain_KO_Q2
BioProject PRJNA310347
SRA SRP069148

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Supplementary file Size Download File type/resource
GSE77447_RAW.tar 9.2 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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