Factor binding and chromatin modification in the promoter of murine Egr1 gene upon induction.
The influence of chromatin on immediate-early gene expression has been studied in a model of Egr1 induction in intact mouse cells. ChIP analysis of factor and RNA polymerase binding reveals that the gene is constitutively poised for transcription in nonstimulated cells, but a repressing chromatin structure hampers productive transcription. Stimulation with phorbol esters results in a transient activation, which starts at 5 min and peaks at 30 min. Quantitative mapping of promoter occupancy by the different factors shows for the first time that no direct competition between SP1 and EGR1 occurs. The phosphorylation of ELK1 and CREB, which involves both the cascades of MEK1/2 and p38 kinases, is required for gene expression, which ceases following the binding of NAB1 and NAB2 to the promoter. The changes in histone acetylation and the differential recruitment of histone-modifying complexes further show the role of chromatin in the activation of this immediate-early gene.
Tur
Gema
G
The Chromatin Laboratory, Department of Biochemistry and Molecular Biology, University of Valencia, Dr Moliner, 50, 46100 Burjassot, Valencia, Spain.
Georgieva
Elena I
EI
Gagete
Andrés
A
López-Rodas
Gerardo
G
Rodríguez
José L
JL
Franco
Luis
L
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C494113:Elk1 protein, mouse; D006657:Histones; C490624:Nab1 protein, mouse; C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D026362:Serum Response Factor; D050807:ets-Domain Protein Elk-1