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Updated: Jul 19, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

14.2K

BRD4 directs mitotic cell division by inhibiting DNA damage

Tiyun Wu, Haitong Hou, Anup Dey

    Biorxiv : the Preprint Server for Biology
    |August 7, 2023
    PubMed

    Insights

    Bromodomain 4 (BRD4) is essential for normal cell growth, regulating cell cycle progression and DNA repair. Its absence causes slow growth, replication failure, and DNA damage in mouse cells.

    Area of Science:

    • Epigenetics
    • Molecular Biology
    • Cell Biology

    Background:

    • Bromodomain 4 (BRD4) is known to regulate transcription and cancer cell proliferation by binding to acetylated histones.
    • The specific role of BRD4 in normal cellular growth and development has not been fully understood.

    Approach:

    • Investigated the function of BRD4 in normal cell growth using mouse embryonic fibroblasts with a conditional Brd4 knockout (KO).
    • Analyzed cell cycle progression, DNA replication, mitosis, and DNA damage in Brd4KO cells compared to wild-type cells.
    • Examined the expression of cell cycle genes, histone genes, centromere/kinetochore proteins, R-loop formation genes, and DNA damage response (DDR) genes.

    Key Points:

    • Brd4KO cells exhibited significantly slower growth, failed to complete DNA replication and mitosis, and showed extensive DNA damage.
    • BRD4 is required for the expression of over 450 cell cycle genes, including those critical for genome replication and chromosomal segregation.
    • BRD4 is essential for the expression of genes involved in R-loop formation and the DNA damage response (DDR).
    • BRD4 constitutively occupies genes regulating R-loop, DDR, and cell cycle progression.

    Conclusions:

    • BRD4 acts as a master regulator of normal cell growth.
    • BRD4 epigenetically marks genes involved in R-loop formation, DNA damage response, and cell cycle progression, ensuring their proper expression and function.

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