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Nucleic Acids Research Advance Access originally published online on December 4, 2008
Nucleic Acids Research 2009 37(2):441-451; doi:10.1093/nar/gkn931
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Nucleic Acids Research, 2009, Vol. 37, No. 2 441-451
© 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

Systematic prediction of control proteins and their DNA binding sites

Valeriy Sorokin1, Konstantin Severinov2,3,4,* and Mikhail S. Gelfand1,5,*

1Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia, 2Waksman Institute, Rutgers, The State University of New Jersey, NJ, USA, 3Institute of Gene Biology, 4Institute of Molecular Genetics and 5A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia

*To whom correspondence should be addressed. Tel: +1 732 445 6095; Fax: +1 732 445 57 35; Email: severik{at}waksman.rutgers.edu

Correspondence may also be addressed to Mikhail S. Gelfand. Tel: +7 495 650 42 25, Fax: +7 495 650 05 79; Email: gelfand{at}iitp.ru

Received September 19, 2008. Revised October 31, 2008. Accepted November 4, 2008.

We present here the results of a systematic bioinformatics analysis of control (C) proteins, a class of DNA-binding regulators that control time-delayed transcription of their own genes as well as restriction endonuclease genes in many type II restriction-modification systems. More than 290 C protein homologs were identified and DNA-binding sites for ~70% of new and previously known C proteins were predicted by a combination of phylogenetic footprinting and motif searches in DNA upstream of C protein genes. Additional analysis revealed that a large proportion of C protein genes are translated from leaderless RNA, which may contribute to time-delayed nature of genetic switches operated by these proteins. Analysis of genetic contexts of newly identified C protein genes revealed that they are not exclusively associated with restriction-modification genes; numerous instances of associations with genes originating from mobile genetic elements were observed. These instances might be vestiges of ancient horizontal transfers and indicate that during evolution ancestral restriction-modification system genes were the sites of mobile elements insertions.


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