Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation

被引：45

作者：

Cuitino, Maria C. ^{[1
]}

Pecot, Thierry ^{[1
]}

Sun, Daokun ^{[1
,2
]}

Kladney, Raleigh ^{[2
]}

Okano-Uchida, Takayuki ^{[1
]}

Shinde, Neelam ^{[3
]}

Saeed, Resham ^{[3
]}

Perez-Castro, Antonio J. ^{[3
]}

Webb, Amy ^{[4
]}

Liu, Tom ^{[4
]}

Bae, Soo In ^{[2
]}

Clijsters, Linda ^{[5
]}

Selner, Nicholas ^{[1
]}

Coppola, Vincenzo ^{[2
]}

Timmers, Cynthia ^{[1
,4
]}

Ostrowski, Michael C. ^{[1
]}

Pagano, Michele ^{[5
,6
]}

Leone, Gustavo ^{[1
]}

机构：

[1] Med Univ South Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC 29425 USA

[2] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Canc Biol & Genet, Columbus, OH 43210 USA

[4] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[5] NYU, Sch Med, Perlmutter Canc Ctr, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[6] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA

来源：

CELL REPORTS | 2019年 / 27卷 / 12期

关键词：

TUMOR SUPPRESSION; S-PHASE; RB/E2F PATHWAY; FAMILY-MEMBER; STEM-CELLS; CANCER; PROLIFERATION; ROLES; MICE; IDENTIFICATION;

D O I：

10.1016/j.celrep.2019.05.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 G(0), G(1)-S, and S-G(2)-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.

引用

页码：3547 / +

页数：19

共 82 条

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