E2F1 induces a G0-G1 reentry transcriptional program without changing chromatin accessibility

Area of Science:

• Cell Biology
• Molecular Biology
• Epigenetics

Background:

• Quiescent cells maintain a non-dividing state by repressing cell-cycle genes through chromatin mechanisms.
• Reentry into the cell cycle requires overcoming this repression, with E2F1 being a known inducer.

Purpose of the Study:

• To elucidate the mechanism by which E2F1 overcomes chromatin-mediated repression to induce cell-cycle reentry.
• To understand the dynamics of transcription factor binding and chromatin accessibility during quiescence exit.

Main Methods:

• Inducible E2F1 expression system
• Time-resolved transcriptomics
• Chromatin immunoprecipitation sequencing (ChIP-seq)
• Biochemical reconstitution assays

Main Results:

• E2F1 expression induced cell-cycle reentry without altering global chromatin accessibility.
• E2F1 harnessed pre-existing, accessible regulatory elements for gene activation.
• Transcriptional activation by E2F1 was accelerated and occurred with limited chromatin remodeling compared to serum stimulation.
• E2F1 directly bound target sites in quiescent cells and accessed DNA within nucleosomes.

Conclusions:

• E2F1 can initiate transcription and cell-cycle reentry by engaging nucleosome-associated DNA without significant chromatin reorganization.
• These findings redefine transcription factor-chromatin interactions during cell fate transitions.
• E2F1 is established as a key regulator of cell-cycle reentry from quiescence.