Transcription and chromatin determinants of de novo DNA methylation timing in oocytes

Epigenetics & Chromatin
Lenka GahurovaGavin Kelsey

Abstract

Gametogenesis in mammals entails profound re-patterning of the epigenome. In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established largely as a consequence of transcription events. Molecular and functional studies have shown that imprinted genes become methylated at different times during oocyte growth; however, little is known about the kinetics of methylation gain genome wide and the reasons for asynchrony in methylation at imprinted loci. Given the predominant role of transcription, we sought to investigate whether transcription timing is rate limiting for de novo methylation and determines the asynchrony of methylation events. Therefore, we generated genome-wide methylation and transcriptome maps of size-selected, growing oocytes to capture the onset and progression of methylation. We find that most sequence elements, including most classes of transposable elements, acquire methylation at similar rates overall. However, methylation of CpG islands (CGIs) is delayed compared with the genome average and there are reproducible differences amongst CGIs in onset of methylation. Although more highly transcribed genes acquire methylation earlier, the major tr...Continue Reading

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Citations

Feb 21, 2018·Biology of Reproduction·Jennifer M SanMiguel, Marisa S Bartolomei
Sep 25, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sebastian CanovasPilar Coy
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Nov 30, 2019·Essays in Biochemistry·Gintarė Sendžikaitė, Gavin Kelsey
Feb 20, 2020·International Journal of Molecular Sciences·Tomas MasekMartin Pospisek
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Mar 10, 2020·F1000Research·Hannah Demond, Gavin Kelsey
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Nov 19, 2021·The Journal of Clinical Endocrinology and Metabolism·Angelo MiliotoHarald Jüppner

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Methods Mentioned

BETA
Illumina sequencing
PBAT
RRBS
RNA-seq
immunoprecipitation
ChIP-seq
PCR

Software Mentioned

custom Perl scripts
Bismark methylation extractor
Trim Galore
ElasiticNet
MEME suite
MEME
TopHat
GOrilla
SeqMonk
Cufflinks

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