Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress

TY - JOUR

T1 - Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress

AU - Fan, Alex Xiucheng

AU - Papadopoulos, Giorgio L

AU - Hossain, Mir A

AU - Lin, I-Ju

AU - Hu, Jianhong

AU - Tang, Tommy Ming

AU - Kilberg, Michael S

AU - Renne, Rolf

AU - Strouboulis, John

AU - Bungert, Jörg

N1 - © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2014/7/8

Y1 - 2014/7/8

N2 - The ubiquitously expressed transcription factor TFII-I exerts both positive and negative effects on transcription. Using biotinylation tagging technology and high-throughput sequencing, we determined sites of chromatin interactions for TFII-I in the human erythroleukemia cell line K562. This analysis revealed that TFII-I binds upstream of the transcription start site of expressed genes, both upstream and downstream of the transcription start site of repressed genes, and downstream of RNA polymerase II peaks at the ATF3 and other stress responsive genes. At the ATF3 gene, TFII-I binds immediately downstream of a Pol II peak located 5 kb upstream of exon 1. Induction of ATF3 expression increases transcription throughout the ATF3 gene locus which requires TFII-I and correlates with increased association of Pol II and Elongin A. Pull-down assays demonstrated that TFII-I interacts with Elongin A. Partial depletion of TFII-I expression caused a reduction in the association of Elongin A with and transcription of the DNMT1 and EFR3A genes without a decrease in Pol II recruitment. The data reveal different interaction patterns of TFII-I at active, repressed, or inducible genes, identify novel TFII-I interacting proteins, implicate TFII-I in the regulation of transcription elongation and provide insight into the role of TFII-I during the response to cellular stress.

AB - The ubiquitously expressed transcription factor TFII-I exerts both positive and negative effects on transcription. Using biotinylation tagging technology and high-throughput sequencing, we determined sites of chromatin interactions for TFII-I in the human erythroleukemia cell line K562. This analysis revealed that TFII-I binds upstream of the transcription start site of expressed genes, both upstream and downstream of the transcription start site of repressed genes, and downstream of RNA polymerase II peaks at the ATF3 and other stress responsive genes. At the ATF3 gene, TFII-I binds immediately downstream of a Pol II peak located 5 kb upstream of exon 1. Induction of ATF3 expression increases transcription throughout the ATF3 gene locus which requires TFII-I and correlates with increased association of Pol II and Elongin A. Pull-down assays demonstrated that TFII-I interacts with Elongin A. Partial depletion of TFII-I expression caused a reduction in the association of Elongin A with and transcription of the DNMT1 and EFR3A genes without a decrease in Pol II recruitment. The data reveal different interaction patterns of TFII-I at active, repressed, or inducible genes, identify novel TFII-I interacting proteins, implicate TFII-I in the regulation of transcription elongation and provide insight into the role of TFII-I during the response to cellular stress.

KW - Activating Transcription Factor 3/genetics

KW - Binding Sites

KW - Biotinylation

KW - Carbon-Nitrogen Ligases/metabolism

KW - DNA Topoisomerases, Type II/metabolism

KW - Elongin

KW - Escherichia coli Proteins/metabolism

KW - Genomics

KW - Humans

KW - K562 Cells

KW - Nuclear Proteins/metabolism

KW - Proteomics

KW - RNA Polymerase II/metabolism

KW - Repressor Proteins/metabolism

KW - Stress, Physiological/genetics

KW - TATA-Binding Protein Associated Factors/metabolism

KW - Transcription Factors/metabolism

KW - Transcription Factors, TFII/metabolism

KW - Transcription Initiation Site

U2 - 10.1093/nar/gku467

DO - 10.1093/nar/gku467

M3 - Article

C2 - 24875474

SN - 0305-1048

VL - 42

SP - 7625

EP - 7641

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 12

ER -