Genome-wide analysis of transcriptional bursting-induced noise in mammalian cells

Hiroshi Ochiai, Tetsutaro Hayashi, Mana Umeda, Mika Yoshimura, Akihito Harada, Yukiko Shimizu, Kenta Nakano, Noriko Saitoh, Hiroshi Kimura, Zhe Liu, Takashi Yamamoto, Tadashi Okamura, Yasuyuki Ohkawa, Itoshi Nikaido

Research output: Contribution to journalArticlepeer-review

Abstract

Transcriptional bursting is stochastic activation and inactivation of promoters, leading to discontinuous production of mRNA, and is considered to be a contributing factor to cell-to-cell heterogeneity in gene expression. However, it remains elusive how the kinetic properties of transcriptional bursting (e.g., burst size, burst frequency, and noise induced by transcriptional bursting) are regulated in mammalian cells. In this study, we performed a genome-wide analysis of transcriptional bursting in mouse embryonic stem cells (mESCs) using single-cell RNA-sequencing. We found that the kinetics of transcriptional bursting was determined by a combination of promoter and gene body binding proteins, including polycomb repressive complex 2 and transcription elongation-related factors. Furthermore, large-scale CRISPR-Cas9-based screening and functional analysis revealed that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncover key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - Aug 15 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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