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Letter

Systematic Characterization of the Zinc-Finger-Containing Proteins in the Mouse Transcriptome

¹Institute for Molecular Bioscience, Brisbane, Australia ²ARC Special Research Centre for Functional and Applied Genomics, Brisbane, Australia ³CRC for Chronic Inflammatory Diseases, Brisbane, Australia ⁴Computational Biology and Bioinformatics Environment ComBinE, Brisbane, Australia ⁵University of Queensland, Brisbane, Australia ⁶Laboratory of Computational Genomics, The Rockefeller University, New York, New York 10021, USA ⁷Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan ⁸Genome Science Laboratory, RIKEN, Hirosawa, Wako, Saitama 351-0198, Japan

Zinc-finger-containing proteins can be classified into evolutionary and functionally divergent protein families that share one or more domains in which a zinc ion is tetrahedrally coordinated by cysteines and histidines. The zinc finger domain defines one of the largest protein superfamilies in mammalian genomes;46 different conserved zinc finger domains are listed in InterPro (http://www.ebi.ac.uk/InterPro). Zinc finger proteins can bind to DNA, RNA, other proteins, or lipids as a modular domain in combination with other conserved structures. Owing to this combinatorial diversity, different members of zinc finger superfamilies contribute to many distinct cellular processes, including transcriptional regulation, mRNA stability and processing, and protein turnover. Accordingly, mutations of zinc finger genes lead to aberrations in a broad spectrum of biological processes such as development, differentiation, apoptosis, and immunological responses. This study provides the first comprehensive classification of zinc finger proteins in a mammalian transcriptome. Specific detailed analysis of the SP/Krüppel-like factors and the E3 ubiquitin-ligase RING-H2 families illustrates the importance of such an analysis for a more comprehensive functional classification of large protein families. We describe the characterization of a new family of C2H2 zinc-finger-containing proteins and a new conserved domain characteristic of this family, the identification and characterization of Sp8, a new member of the Sp family of transcriptional regulators, and the identification of five new RING-H2 proteins.

⁹ Corresponding author.
E-MAIL t.ravasi{at}imb.uq.edu.au; FAX 61-7-3365 4388.

¹⁰ Takahiro Arakawa, Piero Carninci, Jun Kawai, and Yoshihide Hayashizaki.

[Supplemental material is available online at www.genome.org. To facilitate future characterization of this superfamily, we generated a Web-based interface, http://cassandra.visac.uq.edu.au/zf, containing the structural classification of the entire zinc finger data set discussed in this study.]

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