title: Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA.
authors.forename: Alex Xiucheng
authors.initials: AX
authors.lastname: Fan
authors.affiliation: Departmentof Biology, University of Crete, GR1409 Heraklion, Greece Divisionof Molecular Oncology, Biomedical Sciences Research Center "Alexander Fleming", Vari GR 16672, Greece.
authors.forename: Giorgio L
authors.initials: GL
authors.lastname: Papadopoulos
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA.
authors.forename: Mir A
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Lin
authors.affiliation: Departmentof Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, 32610, USA.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA.
authors.forename: Tommy Ming
authors.initials: TM
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kilberg
authors.affiliation: Divisionof Molecular Oncology, Biomedical Sciences Research Center "Alexander Fleming", Vari GR 16672, Greece.
authors.forename: Rolf
authors.initials: R
authors.lastname: Renne
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA Departmentof Biology, University of Crete, GR1409 Heraklion, Greece Divisionof Molecular Oncology, Biomedical Sciences Research Center "Alexander Fleming", Vari GR 16672, Greece Departmentof Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, 32610, USA strouboulis@fleming.gr.
authors.forename: John
authors.initials: J
authors.lastname: Strouboulis
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, Powell Gene Therapy Center, Gainesville, Florida, USA jbungert@ufl.edu.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bungert
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics; D001665:Binding Sites; D019921:Biotinylation; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D000075065:Elongin; D029968:Escherichia coli Proteins / Q000378:metabolism; D023281:Genomics; D006801:Humans; D020014:K562 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D040901:Proteomics; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D051700:Activating Transcription Factor 3; C000616397:ELOA protein, human; D000075065:Elongin; D029968:Escherichia coli Proteins; C104259:GTF2I protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D012319:RNA Polymerase II; D004250:DNA Topoisomerases, Type II; D019731:Carbon-Nitrogen Ligases; C058125:birA protein, E coli