Transcription as a driver of epigenetic transitions in the oocyte
Gavin Kelsey, Babraham Institute
23rd February 2017 at 1:00pm [Download iCalendar / .ics file]
Michael Swann, 7.20
Chromatin organisation is fundamental to genomic regulation, of which histone modifications are an integral part, however, it remains unclear to what extent histone modifications are an instructive component of the epigenetic landscape. The oocyte provides an attractive system to investigate temporal aspects of epigenetic regulation, because of the extensive epigenetic remodelling that occurs in a non-dividing cell; moreover, chromatin states in the oocyte may inform gene regulation in the zygote. Using new ultra low input chromatin immunoprecipitation methods to interrogate histone modifications throughout oogenesis, we observe widespread reprogramming of H3K4me3 in early oocytes, which subsequently accumulates independent of transcription. A consequence of the widespread deposition of H3K4me3 was the generation de novo of bivalent promoters and loss of canonical enhancer marks. Using conditional knock-outs to ablate H3K4me3 or DNA methylation in oocytes revealed, unexpectedly, that DNA methylation was dominant over H3K4me3 deposition. These results suggest that histone remodelling is not a driver of genomic regulation in the oocyte, but reflects transcriptional activity and targeting of DNA methylation.
Host Adrian Bird
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