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Molecular and Cellular Biology, July 2002, p. 5036-5046, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5036-5046.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The ETS Domain Transcription Factor Elk-1 Contains a Novel Class of Repression Domain

School of Biological Sciences, University of Manchester, Manchester M13 9PT,¹ Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom²

Received 16 November 2002/ Returned for modification 9 January 2002/ Accepted 23 April 2002

The ETS domain transcription factor Elk-1 serves as an integration point for different mitogen-activated protein (MAP) kinase pathways. Phosphorylation of Elk-1 by MAP kinases triggers its activation. However, while the activation process is well understood, its downregulation-inactivation is less well characterized. The ETS DNA-binding domain plays a role in the downregulation of Elk-dependent promoter activity following mitogenic activation by recruiting the mSin3A-HDAC complex. Here we have identified a novel evolutionarily conserved repression domain in Elk-1, termed the R motif, which serves to reduce the basal transcriptional activity of Elk-1 and dampen its response to mitogenic signals. This domain is highly potent and portable and can repress transcription in trans. The R motif is related to the CRD1 repression domain in p300 and can functionally replace this domain and confer p21^waf1/cip1 inducibility on p300. However, the R motif acts in a context-dependent manner and is not p21^waf1/cip1 responsive in Elk-1. Thus, the Elk-1 R motif and the p300 CRD1 motif represent a new class of repression domains that are regulated in a context-dependent manner.

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