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Open Access Highly Accessed Research

HIRA dependent H3.3 deposition is required for transcriptional reprogramming following nuclear transfer to Xenopus oocytes

Jerome Jullien1*, Carolina Astrand1, Emmanuelle Szenker2, Nigel Garrett1, Genevieve Almouzni2 and John B Gurdon1

Author Affiliations

1 The Welcome Trust/Cancer Research UK Gurdon Institute, The Henry Welcome building of Cancer and Developmental Biology, and Department of Zoology, Cambridge, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

2 Institute Curie Section de Recherché UMR 218, 26 rue d'Ulm, 75248, Paris Cedex 05, France

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Epigenetics & Chromatin 2012, 5:17  doi:10.1186/1756-8935-5-17

Published: 29 October 2012

Abstract

Background

Nuclear reprogramming is potentially important as a route to cell replacement and drug discovery, but little is known about its mechanism. Nuclear transfer to eggs and oocytes attempts to identify the mechanism of this direct route towards reprogramming by natural components. Here we analyze how the reprogramming of nuclei transplanted to Xenopus oocytes exploits the incorporation of the histone variant H3.3.

Results

After nuclear transplantation, oocyte-derived H3.3 but not H3.2, is deposited on several regions of the genome including rDNA, major satellite repeats, and the regulatory regions of Oct4. This major H3.3 deposition occurs in absence of DNA replication, and is HIRA-and transcription-dependent. It is necessary for the shift from a somatic- to an oocyte-type of transcription after nuclear transfer.

Conclusions

This study demonstrates that the incorporation of histone H3.3 is an early and necessary step in the direct reprogramming of somatic cell nuclei by oocyte. It suggests that the incorporation of histone H3.3 is necessary during global changes in transcription that accompany changes in cell fate.