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 language | English |
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Pages (from-to) | 712-722 |
Number of pages | 11 |
Journal | Journal of Cellular Biochemistry |
Volume | 119 |
Issue number | 1 |
Early online date | 31 Jul 2017 |
DOIs | |
Publication status | Published - 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