Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter.
Transcriptional activation of a gene involves an orchestrated recruitment of components of the basal transcription machinery and intermediate factors, concomitant with an alteration in local chromatin structure generated by posttranslational modifications of histone tails and nucleosome remodeling. We provide here a comprehensive picture of events resulting in transcriptional activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells. This description integrates chromatin remodeling with a kinetic evaluation of cyclical networks of association of 46 transcription factors with the promoter, as determined by chromatin immunoprecipitation assays. We define the concept of a "transcriptional clock" that directs and achieves the sequential and combinatorial assembly of a transcriptionally productive complex on a promoter. Furthermore, the unanticipated findings of key roles for histone deacetylases and nucleosome-remodeling complexes in limiting transcription implies that transcriptional activation is a cyclical process that requires both activating and repressive epigenetic processes.
Métivier
Raphaël
R
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. raphael.metivier@embl-heidelberg.de
Penot
Graziella
G
Hübner
Michael R
MR
Reid
George
G
Brand
Heike
H
Kos
Martin
M
Gannon
Frank
F
D001683:Biological Clocks / Q000235:genetics; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000235:genetics; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D047628:Estrogen Receptor alpha; D004967:Estrogens; D009707:Nucleosomes; D011506:Proteins; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases