E2F coordination of G2/M transcriptional program

Exploratory Score: 0.750 Price: $0.50 endocycling mammalian cells Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting E2F1, E2F2, E2F3, E2F7, E2F8, G2/M phase genes in endocycling mammalian cells. Primary outcome: G2/M gene expression levels

Description

This experiment examined how the two opposing arms of the E2F program coordinate expression of a unique G2/M phase transcriptional program critical for mitosis, karyokinesis, and cytokinesis. The study investigated the transcriptional targets and regulatory mechanisms by which canonical E2F activators and atypical E2F repressors work together to control genes involved in cell division processes. This involved analyzing gene expression patterns of G2/M phase genes in the context of E2F manipulation, demonstrating how the balance between E2F activation and repression determines the expression levels of mitotic machinery components essential for proper cell division versus endoreduplication cycles.

TARGET GENE
E2F1, E2F2, E2F3, E2F7, E2F8, G2/M phase genes
MODEL SYSTEM
endocycling mammalian cells
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
E2F transcriptional program, G2/M cell cycle checkpoint, mitosis regulation
SOURCE
extracted_from_pmid_23064266
PRIMARY OUTCOME
G2/M gene expression levels

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.750 composite

📖 Wiki Pages

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Protocol

E2F Coordination of G2/M Transcriptional Program in Endocycling Cells Protocol

Phase 1: Cell Culture and Synchronization for Endocycle Entry (Days 1-21)

Cell Model: Use primary rat trophoblast giant cells (TGCs) or human placental BeWo cells as models of physiological endocycle. Alternatively, use serum-starved (48h) Human Dermal Fibroblasts (HDFs) re-entering cell cycle in which E2F7/E2F8 dominate.

Endocycle Induction: Culture TGCs in DMEM + 10% FBS. Endocycle entry confirmed via: (a) DNA content (4N-8N by propidium iodide, flow cytometry), (b) absence of cytokinesis (cleavage furrow markers absent), (c) upregulation of E2F7/E2F8 (qRT-PCR).

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Expected Outcomes

Primary Outcomes

E2F Switch: Endocycling cells show dominant expression of E2F7/E2F8 (repressors) and near-absent E2F1-E2F3 (activators) vs. mitotic cells. This E2F regulatory switch drives endocycle gene expression program.

Target Gene Identification: E2F7/E2F8 occupy promoters of G2/M genes (Aurora B kinase, PLK1, Cyclin B1) in endocycling cells, repressing their expression by 60-80% vs. mitotic cells. This explains why endocycling cells arrest in G2 without mitosis.

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Success Criteria

Primary Success Criteria

E2F Expression Pattern: E2F7/E2F8 mRNA must be ≥3-fold higher in endocycling vs. mitotic cells, while E2F1 must be ≤30% of mitotic cell levels (confirmed via qRT-PCR, n≥3).

Target Repression: G2/M genes (Aurora B, PLK1, CCNB1) must show ≥50% lower expression in endocycling vs. mitotic cells (qRT-PCR, p < 0.01).

Secondary Success Criteria

ChIP-seq Validation: E2F7/E2F8 ChIP-seq peaks must be significantly enriched at G2/M gene promoters (≥4-fold over input, q < 0.01) in endocycling cells, confirmed in ≥2 independent ChIP experiments.

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