U2OS shE4F1 transcriptome

Zinc finger (ZnF) proteins represent one of the largest families of human proteins, although most remain uncharacterized. Given that numerous ZnF proteins are able to interact with DNA and poly(ADP-ribose), there is a growing interest in the understanding of their mechanism of action in the maintenance of genome integrity. We now report that the ZnF protein E4F1 is an actor of DNA repair. Indeed, E4F1 is rapidly recruited, in a PARP-dependent manner, to DNA breaks and promotes ATR/CHK1 signaling, DNA-end resection and subsequent homologous recombination. Moreover, we identified E4F1 as a new regulator of the ATP-dependent chromatin remodeling SWI/SNF complex in DNA repair. E4F1 binds to the catalytic subunit BRG1/SMARCA4, and together with PARP-1, mediates its recruitment to DNA lesions. We also report that a proportion of human breast cancers show amplification and overexpression of E4F1 or BRG1 that are mutually exclusive with BRCA1/2 alterations. Together, these results reveal a novel function of E4F1 in the DNA damage response that orchestrates proper signaling and repair of double strand breaks and document a molecular mechanism for its essential role in maintaining genome integrity and cell survival. Overall design: U2OS cells (3 independent pool) were cultured in DMEM 10% FBS and infected with shRNA ctrl or E4F1. RNA were extracted 72h after infection and sequences were obtained with an Illumina NextSeq 500 sequencer.