@article{f9c746c9e6c94fdaa50ce745d350230a,
title = "Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells",
abstract = "Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, the mechanism underlying the regulation of transcriptional bursting kinetics (burst size and frequency) in mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing to analyze the intrinsic noise and mRNA levels for elucidating the transcriptional bursting kinetics in mouse embryonic stem cells. Informatics analyses and functional assays revealed that transcriptional bursting kinetics was regulated by a combination of promoter- and gene body-binding proteins, including the polycomb repressive complex 2 and transcription elongation factors. Furthermore, large-scale CRISPR-Cas9-based screening identified that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncovered the key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.",
author = "Hiroshi Ochiai and Tetsutaro Hayashi and Mana Umeda and Mika Yoshimura and Akihito Harada and Yukiko Shimizu and Kenta Nakano and Noriko Saitoh and Zhe Liu and Takashi Yamamoto and Tadashi Okamura and Yasuyuki Ohkawa and Hiroshi Kimura and Itoshi Nikaido",
note = "Funding Information: We would like to thank T. Miyamoto and T. Fukaya for helpful discussions and Y. Ochiai for technical assistance. We would also like to thank J. Gribnau for providing the hybrid mouse ES cell line F1-21.6 (129Sv-Cast/EiJ, female). We thank A. Matsushima and M. Ishii for their assistance with the infrastructure for the data analysis. This work was supported by the JST PRESTO program (Japan) to H.O. (JPMJPR15F2) and JSPS KAKENHI (Japan) to H.O. (JP18H05531 and JP19K06612), N.S. (JP18H05531), and H.K. and Y.O. (JP18H05527) and partially by JST CREST (Japan) to I.N. (JPMJCR16G3) and H.K. and Y.O. (JPMJCR16G1). The sequence operations of RamDA-seq using HiSeq2500 were supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and Development (AMED). Publisher Copyright: {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jun,
doi = "10.1126/sciadv.aaz6699",
language = "English",
volume = "6",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "25",
}