Faculty Collaboration Database

Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation. Cell Rep 2019 Jun 18;27(12):3547-3560.e5

Date

05/28/2019

Pubmed ID

31130414

Pubmed Central ID

PMC6673649

DOI

10.1016/j.celrep.2019.05.004

Scopus ID

2-s2.0-85067252067 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

Orchestrating cell-cycle-dependent mRNA oscillations is critical to cell proliferation in multicellular organisms. Even though our understanding of cell-cycle-regulated transcription has improved significantly over the last three decades, the mechanisms remain untested in vivo. Unbiased transcriptomic profiling of G₀, G₁-S, and S-G₂-M sorted cells from FUCCI mouse embryos suggested a central role for E2Fs in the control of cell-cycle-dependent gene expression. The analysis of gene expression and E2F-tagged knockin mice with tissue imaging and deep-learning tools suggested that post-transcriptional mechanisms universally coordinate the nuclear accumulation of E2F activators (E2F3A) and canonical (E2F4) and atypical (E2F8) repressors during the cell cycle in vivo. In summary, we mapped the spatiotemporal expression of sentinel E2F activators and canonical and atypical repressors at the single-cell level in vivo and propose that two distinct E2F modules relay the control of gene expression in cells actively cycling (E2F3A-8-4) and exiting the cycle (E2F3A-4) during mammalian development.

Author List

Cuitiño MC, Pécot T, Sun D, Kladney R, Okano-Uchida T, Shinde N, Saeed R, Perez-Castro AJ, Webb A, Liu T, Bae SI, Clijsters L, Selner N, Coppola V, Timmers C, Ostrowski MC, Pagano M, Leone G

Author

Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Cycle
Cell Cycle Proteins
Cell Differentiation
Cell Proliferation
Cells, Cultured
E2F3 Transcription Factor
E2F4 Transcription Factor
Female
Gene Expression Regulation
Male
Mice
Mice, Knockout
Promoter Regions, Genetic
Repressor Proteins
Transcriptome