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

Overview of attention for article published in Epigenetics & Chromatin, May 2017
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Title
Transcription and chromatin determinants of de novo DNA methylation timing in oocytes
Published in
Epigenetics & Chromatin, May 2017
DOI 10.1186/s13072-017-0133-5
Pubmed ID
Authors

Lenka Gahurova, Shin-ichi Tomizawa, Sébastien A. Smallwood, Kathleen R. Stewart-Morgan, Heba Saadeh, Jeesun Kim, Simon R. Andrews, Taiping Chen, Gavin 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 transitions in the oocyte transcriptome occur well before the de novo methylation phase, indicating that transcription is generally not rate limiting in conferring permissiveness to DNA methylation. Instead, CGI methylation timing negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin remodelling as a major determinant of methylation timing. We also identified differential enrichment of transcription factor binding motifs in CGIs acquiring methylation early or late in oocyte growth. By combining these parameters into multiple regression models, we were able to account for about a fifth of the variation in methylation timing of CGIs. Finally, we show that establishment of non-CpG methylation, which is prevalent in fully grown oocytes, and methylation over non-transcribed regions, are later events in oogenesis. These results do not support a major role for transcriptional transitions in the time of onset of DNA methylation in the oocyte, but suggest a model in which sequences least dependent on chromatin remodelling are the earliest to become permissive for methylation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 98 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 98 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 23%
Researcher 16 16%
Student > Bachelor 9 9%
Student > Master 7 7%
Student > Doctoral Student 6 6%
Other 14 14%
Unknown 23 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 45 46%
Agricultural and Biological Sciences 21 21%
Engineering 3 3%
Social Sciences 2 2%
Business, Management and Accounting 1 1%
Other 5 5%
Unknown 21 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 May 2017.
All research outputs
#7,229,289
of 23,577,654 outputs
Outputs from Epigenetics & Chromatin
#294
of 574 outputs
Outputs of similar age
#111,425
of 311,261 outputs
Outputs of similar age from Epigenetics & Chromatin
#10
of 16 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 574 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 311,261 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 16 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.