Nucleic Acids Research Advance Access originally published online on March 11, 2008
Nucleic Acids Research 2008 36(8):2594-2607; doi:10.1093/nar/gkn099
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Nucleic Acids Research, 2008, Vol. 36, No. 8 2594-2607
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1
Centre for Biochemistry and Cell Biology, and School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK
*To whom correspondence should be addressed. Tel: +44 115 82 30 120; Fax: +44 115 82 30 142; Email: peter.shaw{at}nottingham.ac.uk
Received January 21, 2008. Revised February 21, 2008. Accepted February 21, 2008.
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.
Present address: Hong-Mei Zhang, Ningxia Medical College, Yinchuan, Ningxia, China
Glenn Hodgson, Environmental Science and Research Ltd, Wellington, New Zealand
Stéphanie Vougier, Sanofi-Aventis, Paris, France
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors