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

TY - JOUR

T1 - Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci

AU - Shen, Yong

AU - Nar, Rukiye

AU - Fan, Alex X

AU - Aryan, Mahmoud

AU - Hossain, Mir A

AU - Gurumurthy, Aishwarya

AU - Wassel, Paul C

AU - Tang, Ming

AU - Lu, Jianrong

AU - Strouboulis, John

AU - Bungert, Jörg

N1 - © 2017 Wiley Periodicals, Inc.

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - Cell Cycle

KW - Cell Cycle Proteins/genetics

KW - Cell Proliferation

KW - Chromatin Immunoprecipitation

KW - Computational Biology/methods

KW - E2F Transcription Factors/genetics

KW - Humans

KW - K562 Cells

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - Transcription Factors, TFII/genetics

U2 - 10.1002/jcb.26235

DO - 10.1002/jcb.26235

M3 - Article

C2 - 28657656

SN - 0730-2312

VL - 119

SP - 712

EP - 722

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

IS - 1

ER -