Chromatin Accessibility Impacts Transcriptional Reprogramming in Oocytes
Kei Miyamoto,
Khoi T. Nguyen,
George E. Allen,
Jerome Jullien,
Dinesh Kumar,
Tomoki Otani,
Charles R. Bradshaw,
Frederick J. Livesey,
Manolis Kellis,
John B. Gurdon
Affiliations
Kei Miyamoto
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan; Corresponding author
Khoi T. Nguyen
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
George E. Allen
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Jerome Jullien
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Dinesh Kumar
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Tomoki Otani
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Charles R. Bradshaw
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Frederick J. Livesey
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom
Manolis Kellis
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Corresponding author
John B. Gurdon
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Corresponding author
Summary: 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. : Miyamoto et al. show genome-wide changes in chromatin accessibility during transcriptional reprogramming in oocytes using the frog nuclear transfer system. They demonstrate that donor cell chromatin states affect transcriptional reprogramming and changes in open chromatin during reprogramming are associated with specific transcription factors. Keywords: open chromatin, transcriptional activation, reprogramming, nuclear transfer
