title: Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery.
abstract: Transcription factors play an important role in orchestrating the activation of specific networks of genes through targeting their proximal promoter and distal enhancer regions. However, it is unclear how the specificity of downstream responses is maintained by individual members of transcription-factor families and, in most cases, what their target repertoire is. We have used ChIP-chip analysis to identify the target genes of the ETS-domain transcription factor ELK1. Two distinct modes of ELK1 target gene selection are identified; the first involves redundant promoter binding with other ETS-domain family members; the second occurs through combinatorial binding with a second transcription factor SRF, which specifies a unique group of target genes. One of the most prominent groups of genes forming the ELK1 target network includes classes involved in core gene expression control, namely, components of the basal transcriptional machinery, the spliceosome and the ribosome. Amongst the set of genes encoding the basal transcription machinery components, are a functionally linked subset of GTFs and TAFs. Our study, therefore, reveals an unsuspected level of coordinate regulation of components of the core gene expression control machinery and also identifies two different modes of promoter targeting through binding with a second transcription factor or redundant binding with other ETS-domain family members.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Boros
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Donaldson
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Zaneta A
authors.initials: ZA
authors.lastname: Odrowaz
authors.forename: Leo
authors.initials: L
authors.lastname: Zeef
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lupien
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Meyer
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D050807:ets-Domain Protein Elk-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; D051268:GA-Binding Protein Transcription Factor; C495661:GABPA protein, human; D026362:Serum Response Factor; D050807:ets-Domain Protein Elk-1; D008156:Luciferases
references.citation: Nucleic Acids Res. 1995 Nov 25;23(22):4698-706
references.pmid: 8524663
references.citation: Mol Cell Biol. 1994 May;14(5):3283-91
references.pmid: 8164681
references.citation: Cell. 1992 Feb 7;68(3):597-612
references.pmid: 1339307
references.citation: Mol Cell. 2008 Mar 28;29(6):780-5
references.pmid: 18374651
references.citation: Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37
references.pmid: 11715049
references.citation: Genome Biol. 2003;4(5):P3
references.pmid: 12734009
references.citation: EMBO J. 2001 Jun 15;20(12):3018-28
references.pmid: 11406578
references.citation: Genes Dev. 2007 Sep 1;21(17):2137-49
references.pmid: 17704303
references.citation: Mol Cell Biol. 1995 Feb;15(2):1049-59
references.pmid: 7823920
references.citation: Mol Cell Biol. 2009 Jan;29(1):172-86
references.pmid: 18955504
references.citation: Nature. 2004 Nov 25;432(7016):517-22
references.pmid: 15565157
references.citation: Genes Dev. 2007 Aug 1;21(15):1882-94
references.pmid: 17652178
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12457-62
references.pmid: 16895995
references.citation: Nat Methods. 2008 Sep;5(9):829-34
references.pmid: 19160518
references.citation: Nucleic Acids Res. 2004 Oct 21;32(18):5693-702
references.pmid: 15498926
references.citation: Pigment Cell Res. 2007 Dec;20(6):466-84
references.pmid: 17935490
references.citation: Curr Opin Cell Biol. 2007 Apr;19(2):142-9
references.pmid: 17303404
references.citation: Nature. 1992 Jul 30;358(6385):414-7
references.pmid: 1322499
references.citation: Mol Cell Biol. 2007 Jan;27(1):54-64
references.pmid: 17074809
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):397-404
references.pmid: 12702545
references.citation: EMBO J. 1995 Jun 1;14(11):2589-601
references.pmid: 7540136
references.citation: Genes Dev. 2006 Jun 1;20(11):1405-28
references.pmid: 16751179
references.citation: EMBO J. 1992 Dec;11(12):4631-40
references.pmid: 1425594
references.citation: Biochem Soc Trans. 2002 Apr;30(2):1-9
references.pmid: 12023815
references.citation: Gene. 2003 Nov 27;320:3-21
references.pmid: 14597384
references.citation: Chem Biol Interact. 2008 Mar 27;172(2):125-40
references.pmid: 18241849
references.citation: Cell. 2005 Jul 15;122(1):33-43
references.pmid: 16009131
references.citation: Genome Res. 2004 Aug;14(8):1562-74
references.pmid: 15256515
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12347-52
references.pmid: 16895980
references.citation: Crit Rev Biochem Mol Biol. 2006 May-Jun;41(3):105-78
references.pmid: 16858867
references.citation: Gene. 2000 Jan 25;242(1-2):1-13
references.pmid: 10721692
references.citation: Genomics. 1992 Aug;13(4):1322-4
references.pmid: 1505965
references.citation: Int J Biochem Cell Biol. 2003 Aug;35(8):1210-26
references.pmid: 12757758
references.citation: Mol Cell. 2004 Dec 22;16(6):867-80
references.pmid: 15610731