Chromatin Accessibility Impacts Transcriptional Reprogramming in Oocytes.

Authors
Miyamoto, Kei 
Nguyen, Khoi T 
Allen, George E 
Kumar, Dinesh 

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Article
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Abstract

Oocytes have a remarkable ability to reactivate silenced genes in somatic cells. However, it is not clear how the chromatin architecture of somatic cells affects this transcriptional reprogramming. Here, we investigated the relationship between the chromatin opening and transcriptional activation. We reveal changes in chromatin accessibility and their relevance to transcriptional reprogramming after transplantation of somatic nuclei into Xenopus oocytes. Genes that are silenced, but have pre-existing open transcription start sites in donor cells, are prone to be activated after nuclear transfer, suggesting that the chromatin signature of somatic nuclei influences transcriptional reprogramming. There are also activated genes associated with new open chromatin sites, and transcription factors in oocytes play an important role in transcriptional reprogramming from such genes. Finally, we show that genes resistant to reprogramming are associated with closed chromatin configurations. We conclude that chromatin accessibility is a central factor for successful transcriptional reprogramming in oocytes.

Publication Date
2018-07-10
Online Publication Date
2018-07-11
Acceptance Date
2018-06-07
Keywords
nuclear transfer, open chromatin, reprogramming, transcriptional activation, Animals, Cellular Reprogramming, Chromatin, Fibroblasts, Mice, Oocytes, Promoter Regions, Genetic, Sequence Analysis, DNA, Transcription Factors, Transcription Initiation Site, Transcription, Genetic, Transcriptional Activation, Transposases, Xenopus laevis
Journal Title
Cell Rep
Journal ISSN
2211-1247
2211-1247
Volume Title
24
Publisher
Elsevier BV
Sponsorship
Wellcome Trust (101050/Z/13/Z)
Wellcome Trust (092096/Z/10/Z)
Medical Research Council (MR/K011022/1)
Cancer Research Uk (None)
Medical Research Council (MR/L023784/2)
Medical Research Council (MR/L023784/1)