Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery

被引:110
作者
Boros, Joanna [1 ]
Donaldson, Ian J. [1 ]
O'Donnell, Amanda [1 ]
Odrowaz, Zaneta A. [1 ]
Zeef, Leo [1 ]
Lupien, Mathieu [2 ,3 ,4 ]
Meyer, Clifford A. [5 ,6 ]
Liu, X. Shirley [5 ,6 ]
Brown, Myles [2 ,3 ,4 ]
Sharrocks, Andrew D. [1 ]
机构
[1] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
[2] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
基金
英国惠康基金;
关键词
TRANSCRIPTION FACTORS ELK-1; TERNARY COMPLEX FACTORS; SERUM RESPONSE FACTOR; EXPRESSION; SAP-1; SRF;
D O I
10.1101/gr.093047.109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1963 / 1973
页数:11
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