Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci

Yong Shen, Rukiye Nar, Alex X Fan, Mahmoud Aryan, Mir A Hossain, Aishwarya Gurumurthy, Paul C Wassel, Ming Tang, Jianrong Lu, John Strouboulis, Jörg Bungert

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C, and CDC27. Inhibition of TFII-I expression led to a decrease in gene expression and in the association of E2F4 and E2F6 with these gene loci in human erythroleukemia K562 cells. Finally, TFII-I deficiency reduced the proliferation of K562 cells and increased the sensitivity toward doxorubicin toxicity. The results uncover novel interactions between TFII-I and E2Fs and suggest that TFII-I mediates E2F function at specific cell cycle genes.

    Original languageEnglish
    Pages (from-to)712-722
    Number of pages11
    JournalJournal of Cellular Biochemistry
    Volume119
    Issue number1
    Early online date31 Jul 2017
    DOIs
    Publication statusPublished - Jan 2018

    Keywords

    • Cell Cycle
    • Cell Cycle Proteins/genetics
    • Cell Proliferation
    • Chromatin Immunoprecipitation
    • Computational Biology/methods
    • E2F Transcription Factors/genetics
    • Humans
    • K562 Cells
    • Promoter Regions, Genetic
    • Protein Binding
    • Transcription Factors, TFII/genetics

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