Molecular Biology and Evolution 19:2118-2130 (2002)
© 2002 Society for Molecular Biology and Evolution
KRAB Zinc Finger Proteins: An Analysis of the Molecular Mechanisms Governing Their Increase in Numbers and Complexity During Evolution
*The Department of Cell and Molecular Biology, Uppsala University;
The Biomedical Center, Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences;
Medical Products Agency, Uppsala
Krüppel-related zinc finger proteins, with 564 members in the human genome, probably constitute the largest individual family of transcription factors in mammals. Approximately 30% of these proteins carry a potent repressor domain called the Krüppel associated box (KRAB). Depending on the structure of the KRAB domain, these proteins have been further divided into three subfamilies (A + B, A + b, and A only). In addition, some KRAB zinc finger proteins contain another conserved motif called SCAN. To study their molecular evolution, an extensive comparative analysis of a large panel of KRAB zinc finger genes was performed. The results show that both the KRAB A + b and the KRAB A subfamilies have their origin in a single member or a few closely related members of the KRAB A + B family. The KRAB A + B family is also the most prevalent among the KRAB zinc finger genes. Furthermore, we show that internal duplications of individual zinc finger motifs or blocks of several zinc finger motifs have occurred quite frequently within this gene family. However, zinc finger motifs are also frequently lost from the open reading frame, either by functional inactivation by point mutations or by the introduction of a stop codon. The introduction of a stop codon causes the exclusion of part of the zinc finger region from the coding region and the formation of graveyards of degenerate zinc finger motifs in the 3'-untranslated region of these genes. Earlier reports have shown that duplications of zinc finger genes commonly occur throughout evolution. We show that there is a relatively low degree of sequence conservation of the zinc finger motifs after these duplications. In many cases this may cause altered binding specificities of the transcription factors encoded by these genes. The repetitive nature of the zinc finger region and the structural flexibility within the zinc finger motif make these proteins highly adaptable. These factors may have been of major importance for their massive expansion in both number and complexity during metazoan evolution.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Wiznerowicz, J. Jakobsson, J. Szulc, S. Liao, A. Quazzola, F. Beermann, P. Aebischer, and D. Trono The Kruppel-associated Box Repressor Domain Can Trigger de Novo Promoter Methylation during Mouse Early Embryogenesis J. Biol. Chem., November 23, 2007; 282(47): 34535 - 34541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Yang, S. M. O'Herrin, J. Wu, S. Reagan-Shaw, Y. Ma, K. M.R. Bhat, C. Gravekamp, V. Setaluri, N. Peters, F. M. Hoffmann, et al. MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines Cancer Res., October 15, 2007; 67(20): 9954 - 9962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang and C. Wood The Transcriptional Repressor K-RBP Modulates RTA-Mediated Transactivation and Lytic Replication of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., June 15, 2007; 81(12): 6294 - 6306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. X. Jin, H. O'Geen, S. Iyengar, R. Green, and P. J. Farnham Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches Genome Res., June 1, 2007; 17(6): 807 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H. Mascle, D. Germain-Desprez, P. Huynh, P. Estephan, and M. Aubry Sumoylation of the Transcriptional Intermediary Factor 1beta (TIF1beta), the Co-repressor of the KRAB Multifinger Proteins, Is Required for Its Transcriptional Activity and Is Modulated by the KRAB Domain J. Biol. Chem., April 6, 2007; 282(14): 10190 - 10202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Birtle and C. P. Ponting Meisetz and the birth of the KRAB motif Bioinformatics, December 1, 2006; 22(23): 2841 - 2845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Huntley, D. M. Baggott, A. T. Hamilton, M. Tran-Gyamfi, S. Yang, J. Kim, L. Gordon, E. Branscomb, and L. Stubbs A comprehensive catalog of human KRAB-associated zinc finger genes: Insights into the evolutionary history of a large family of transcriptional repressors Genome Res., May 1, 2006; 16(5): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Hamilton, S. Huntley, M. Tran-Gyamfi, D. M. Baggott, L. Gordon, and L. Stubbs Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes Genome Res., May 1, 2006; 16(5): 584 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Oh, Y. Li, and Y.-F. C. Lau Sry Associates with the Heterochromatin Protein 1 Complex by Interacting with a KRAB Domain Protein Biol Reprod, February 1, 2005; 72(2): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liu, H. Walch, S. Wu, and A. Grigoriev Significant expansion of exon-bordering protein domains during animal proteome evolution Nucleic Acids Res., January 7, 2005; 33(1): 95 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Khetchoumian, M. Teletin, M. Mark, T. Lerouge, M. Cervino, M. Oulad-Abdelghani, P. Chambon, and R. Losson TIF1{delta}, a Novel HP1-interacting Member of the Transcriptional Intermediary Factor 1 (TIF1) Family Expressed by Elongating Spermatids J. Biol. Chem., November 12, 2004; 279(46): 48329 - 48341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ganss and A. Jheon ZINC FINGER TRANSCRIPTION FACTORS IN SKELETAL DEVELOPMENT Crit. Rev. Oral. Biol. Med., September 1, 2004; 15(5): 282 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Nielsen, P. Jorgensen, T. Lerouge, M. Cervino, P. Chambon, and R. Losson Nizp1, a Novel Multitype Zinc Finger Protein That Interacts with the NSD1 Histone Lysine Methyltransferase through a Unique C2HR Motif Mol. Cell. Biol., June 15, 2004; 24(12): 5184 - 5196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. D. Alonso, G. Zoidl, C. Taveggia, F. Bosse, C. Zoidl, M. Rahman, E. Parmantier, C. H. Dean, B. S. Harris, L. Wrabetz, et al. Identification and Characterization of ZFP-57, a Novel Zinc Finger Transcription Factor in the Mammalian Peripheral Nervous System J. Biol. Chem., June 11, 2004; 279(24): 25653 - 25664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Waxman and J. L. Celenza Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed Genes & Dev., November 1, 2003; 17(21): 2607 - 2613. [Full Text] [PDF]
|
|
|
|
|
|
C. J. Krebs, L. K. Larkins, R. Price, K. M. Tullis, R. D. Miller, and D. M. Robins Regulator of sex-limitation (Rsl) encodes a pair of KRAB zinc-finger genes that control sexually dimorphic liver gene expression Genes & Dev., November 1, 2003; 17(21): 2664 - 2674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Kent, R. Baertsch, A. Hinrichs, W. Miller, and D. Haussler Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes PNAS, September 30, 2003; 100(20): 11484 - 11489. [Abstract] [Full Text] [PDF]
|
|