Proteomics

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TRANSCRIPTIONAL ACTIVATION BY E2F4 INDEPENDENT OF THE RB FAMILY


ABSTRACT: E2F transcription factors are central regulators of cell cycle progression and cell fate decisions in mammalian cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. E2F4 often represents the predominant E2F activity in cells. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. Importantly, this role for E2F4 is completely independent of the RB family. Accordingly, an unbiased analysis of the E2F4 interactome shows that E2F4 functionally interacts with chromatin regulators associated with gene activation in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that reveal novel insights into the biology of rapidly dividing cell types.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Embryo, Retinal Pigment Epithelial Cell, Embryonic Stem Cell, Retinal Pigment Epithelium Cell

SUBMITTER: Janos Demeter  

LAB HEAD: Julien Sage

PROVIDER: PXD008796 | Pride | 2019-04-26

REPOSITORIES: Pride

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Publications

E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family.

Hsu Jenny J   Arand Julia J   Chaikovsky Andrea A   Mooney Nancie A NA   Demeter Janos J   Brison Caileen M CM   Oliverio Romane R   Vogel Hannes H   Rubin Seth M SM   Jackson Peter K PK   Sage Julien J  

Nature communications 20190703 1


E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the exp  ...[more]

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