Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1.
Many eukaryotic genes are acutely regulated by extra-cellular signals. The c-fos serum response element (SRE) mediates transcriptional activation in response to mitogens through serum response factor (SRF)-dependent recruitment of Elk-1, a mitogen-activated protein kinase (MAPK)-responsive transcription factor. How subsequent events at SRE promoters stimulate initiation of transcription has yet to be fully resolved. Here we show that extra-cellular signal-regulated kinase (ERK) and mitogen and stress-activated kinase (MSK) are recruited to SRE promoter complexes in vitro and in vivo. Their recruitment in vitro correlates with Elk-1 binding and for ERK the D domain/KIM of Elk-1 is specifically involved. In vivo, recruitment of ERK and MSK is stimulated by mitogens, correlates with histone H3 phosphorylation and is impaired by Elk-1 knockdown. Immunocytochemistry and confocal microscopy reveal that ERK appears to associate to some extent with initiating rather than elongating RNA polymerase II. Taken together, our data add to the body of evidence implying that ERK and related MAPKs may fulfil a generic role at the promoters of acutely regulated genes.
Zhang
Hong-Mei
HM
Centre for Biochemistry and Cell Biology, and School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Li
Li
L
Papadopoulou
Nektaria
N
Hodgson
Glenn
G
Evans
Emma
E
Galbraith
Matthew
M
Dear
Mark
M
Vougier
Stéphanie
S
Saxton
Janice
J
Shaw
Peter E
PE
D020816:Amino Acid Motifs; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology; D051766:Early Growth Response Protein 1 / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism*; D016762:Genes, fos; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000032:analysis; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D027602:Serum Response Element; D050807:ets-Domain Protein Elk-1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D051766:Early Growth Response Protein 1; D008934:Mitogens; D050807:ets-Domain Protein Elk-1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D012319:RNA Polymerase II