Chromatin Accessibility Impacts Transcriptional Reprogramming in Oocytes

Manolis Kellis,Jerome Jullien,Tomoki Otani,Charles R. Bradshaw,Kei Miyamoto,John B. Gurdon,Frederick J. Livesey,Dinesh Kumar,Khoi T. Nguyen,George E. Allen

doi:10.1016/j.celrep.2018.06.030

Abstract

SummaryOocytes 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.

Highlights

Transcriptional activation is pivotal for cell fate changes and is modulated by the access of chromatin- and transcriptionrelated factors to gene regulatory regions such as promoters and enhancers
We find that chromatin states of donor cells profoundly affect transcriptional reprogramming, oocytes have an ability to open up gene regulatory regions
Optimization and Evaluation of ATAC-Seq for Analyzing Cells Transplanted into Oocytes Somatic cell nuclei transferred into oocytes have different characteristics from conventional cultured cells, in that only a small number of cells can be prepared, and those cells are difficult to permeabilize

Summary

Graphical Abstract

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. 2018, Cell Reports 24, 304–311 July 10, 2018 a 2018 The Authors.

SUMMARY

INTRODUCTION

RESULTS AND DISCUSSION

EXPERIMENTAL PROCEDURES