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Nucleic Acids Research Advance Access originally published online on November 27, 2006
Nucleic Acids Research 2006 34(22):6505-6520; doi:10.1093/nar/gkl888
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Nucleic Acids Research, 2006, Vol. 34, No. 22 6505-6520
© 2006 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.


Genomics

The natural history of the WRKY–GCM1 zinc fingers and the relationship between transcription factors and transposons

M. Madan Babu1,2,{dagger},*, Lakshminarayan M. Iyer1,{dagger}, S. Balaji1 and L. Aravind1,*

1 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD 20894, USA 2 MRC Laboratory of Molecular Biology Hills Road, Cambridge CB2 2QH, UK

*To whom correspondence should be addressed. Tel: +1 301 594 2445; Fax: +1 301 480 9241; Email: madanm{at}mrc-lmb.cam.ac.uk or aravind{at}ncbi.nlm.nih.gov

Received June 29, 2006. Revised October 4, 2006. Accepted October 9, 2006.

WRKY and GCM1 are metal chelating DNA-binding domains (DBD) which share a four stranded fold. Using sensitive sequence searches, we show that this WRKY–GCM1 fold is also shared by the FLYWCH Zn-finger domain and the DBDs of two classes of Mutator-like element (MULE) transposases. We present evidence that they share a stabilizing core, which suggests a possible origin from a BED finger-like intermediate that was in turn ultimately derived from a C2H2 Zn-finger domain. Through a systematic study of the phyletic pattern, we show that this WRKY–GCM1 superfamily is a widespread eukaryote-specific group of transcription factors (TFs). We identified several new members across diverse eukaryotic lineages, including potential TFs in animals, fungi and Entamoeba. By integrating sequence, structure, gene expression and transcriptional network data, we present evidence that at least two major global regulators belonging to this superfamily in Saccharomyces cerevisiae (Rcs1p and Aft2p) have evolved from transposons, and attained the status of transcription regulatory hubs in recent course of ascomycete yeast evolution. In plants, we show that the lineage-specific expansion of WRKY–GCM1 domain proteins acquired functional diversity mainly through expression divergence rather than by protein sequence divergence. We also use the WRKY–GCM1 superfamily as an example to illustrate the importance of transposons in the emergence of new TFs in different lineages.


{dagger}The authors wish it to be known that, in their opinion the first two authors should be regarded as joint First Authors


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