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A novel Krüppel-associated box identified in a panel of mammalian zinc finger proteins

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Abstract

Krüppel-related zinc finger proteins probably constitute the largest individual family of transcription factors in mammals. These proteins often carry a potent repressor domain called the Krüppel Associated Box (KRAB), which is known to effectively repress transcription through interaction with transcriptional intermediary factor 1β (TIF1β). Here we report the isolation and characterization of a novel human KRAB A zinc finger protein, HZF12. The gene encoding HZF12 is located on Chromosome (Chr) 19p13.11-p12, and a 4.4-kb transcript from this gene is expressed in a variety of adult and fetal tissues. Two additional, larger transcripts are expressed in testis only. Interestingly, the KRAB A domain of HZF12 is followed by a 21-amino acid domain, encoded by a separate exon. This domain, which we designate KRAB C, was also identified in more than 25 additional human, mouse, and rat KRAB zinc finger proteins. On the basis of results from a previous study, we conclude that this novel KRAB domain strengthens the interaction with TIF1β, thereby improving the ability of these KRAB zinc finger proteins to recruit TIF1β to specific sites.

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References

  1. M Abrink M Aveskogh L Hellman (1995) ArticleTitleIsolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937. DNA Cell Biol 14 125–136 Occurrence Handle1:STN:280:ByqC28bislU%3D Occurrence Handle7865130

    CAS  PubMed  Google Scholar 

  2. M Abrink JA Ortiz C Mark C Sanchez C Looman et al. (2001) ArticleTitleConserved interaction between distinct Kruppel-associated box domains and the transcriptional intermediary factor 1 beta. Proc Natl Acad Sci USA 98 1422–1426 Occurrence Handle10.1073/pnas.041616998 Occurrence Handle1:CAS:528:DC%2BD3MXhsVWjt78%3D Occurrence Handle11171966

    Article  CAS  PubMed  Google Scholar 

  3. EJ Bellefroid DA Poncelet PJ Lecocq O Revelant JA Martial (1991) ArticleTitleThe evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci USA 88 3608–3612 Occurrence Handle1:CAS:528:DyaK38Xhslegtw%3D%3D Occurrence Handle2023909

    CAS  PubMed  Google Scholar 

  4. C Combet C Blanchet C Geourjon G Deleage (2000) ArticleTitleNPS@: network protein sequence analysis. Trends Biochem Sci 25 147–150 Occurrence Handle1:CAS:528:DC%2BD3cXhsleiu7Y%3D

    CAS  Google Scholar 

  5. JA Cuff ME Clamp AS Siddiqui M Finlay GJ Barton (1998) ArticleTitleJPred: a consensus secondary structure prediction server. Bioinformatics 14 892–893 Occurrence Handle10.1093/bioinformatics/14.10.892 Occurrence Handle1:CAS:528:DyaK1MXht1yisb4%3D Occurrence Handle9927721

    Article  CAS  PubMed  Google Scholar 

  6. P Dehal P Predki AS Olsen A Kobayashi P Folta et al. (2001) ArticleTitleHuman chromosome 19 and related regions in mouse: conservative and lineage-specific evolution. Science 293 104–111 Occurrence Handle10.1126/science.1060310 Occurrence Handle1:CAS:528:DC%2BD3MXltFCntbw%3D Occurrence Handle11441184

    Article  CAS  PubMed  Google Scholar 

  7. JR Friedman WJ Fredericks DE Jensen DW Speicher XP Huang et al. (1996) ArticleTitleKAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev 10 2067–2078 Occurrence Handle1:CAS:528:DyaK28XlsVaqt7k%3D Occurrence Handle8769649

    CAS  PubMed  Google Scholar 

  8. M Hirose (1999) ArticleTitleThe role of Wilms’ tumor genes. J Med Invest 46 130–140 Occurrence Handle1:STN:280:DC%2BD3c7ltF2hsQ%3D%3D Occurrence Handle10687307

    CAS  PubMed  Google Scholar 

  9. SS Kim YM Chen E O’Leary R Witzgall M Vidal et al. (1996) ArticleTitleA novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc Natl Acad Sci USA 93 15299–15304 Occurrence Handle10.1073/pnas.93.26.15299 Occurrence Handle1:CAS:528:DyaK2sXnt1eg Occurrence Handle8986806

    Article  CAS  PubMed  Google Scholar 

  10. ES Lander LM Linton B Birren C Nusbaum MC Zody et al. (2001) ArticleTitleInitial sequencing and analysis of the human genome. Nature 409 860–921 Occurrence Handle1:CAS:528:DC%2BD3MXhsFCjtLc%3D Occurrence Handle11237011

    CAS  PubMed  Google Scholar 

  11. C Looman M Abrink C Mark L Hellman (2002) ArticleTitleKRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers and complexity during evolution. Mol Biol Evol 19 2118–2130 Occurrence Handle1:CAS:528:DC%2BD38Xps12hs7w%3D Occurrence Handle12446804

    CAS  PubMed  Google Scholar 

  12. JF Margolin JR Friedman WK Meyer H Vissing HJ Thiesen et al. (1994) ArticleTitleKruppel-associated boxes are potent transcriptional repression domains. Proc Natl Acad Sci USA 91 4509–4513 Occurrence Handle1:CAS:528:DyaK2cXltVWjt7s%3D Occurrence Handle8183939

    CAS  PubMed  Google Scholar 

  13. C Mark M Abrink L Hellman (1999) ArticleTitleComparative analysis of KRAB zinc finger proteins in rodents and man; evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes. DNA Cell Biol 18 381–396 Occurrence Handle10.1089/104454999315277 Occurrence Handle1:CAS:528:DyaK1MXjsFyqtLw%3D Occurrence Handle10360839

    Article  CAS  PubMed  Google Scholar 

  14. C Mark C Looman M Abrink L Hellman (2001) ArticleTitleMolecular cloning and preliminary functional analysis of two novel human KRAB zinc finger proteins, HKr18 and HKr19. DNA Cell Biol 20 275–286 Occurrence Handle1:CAS:528:DC%2BD3MXktVWhur4%3D Occurrence Handle11410164

    CAS  PubMed  Google Scholar 

  15. P Moosmann O Georgiev B Le Douarin JP Bourquin W Schaffner (1996) ArticleTitleTranscriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Nucleic Acids Res 24 4859–4867 Occurrence Handle10.1093/nar/24.24.4859 Occurrence Handle1:CAS:528:DyaK2sXjvFykug%3D%3D Occurrence Handle9016654

    Article  CAS  PubMed  Google Scholar 

  16. AL Nielsen JA Ortiz J You AM Oulad R Khechumian et al. (1999) ArticleTitleInteraction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. EMBO J 18 6385–6395 Occurrence Handle1:CAS:528:DyaK1MXns1Ortr0%3D Occurrence Handle10562550

    CAS  PubMed  Google Scholar 

  17. DA Poncelet EJ Bellefroid PV Bastiaens MA Demoitie JC Marine et al. (1998) ArticleTitleFunctional analysis of ZNF85 KRAB zinc finger protein, a member of the highly homologous ZNF91 family. DNA Cell Biol 17 931–943 Occurrence Handle1:CAS:528:DyaK1cXnvVGqu7s%3D Occurrence Handle9839802

    CAS  PubMed  Google Scholar 

  18. R Rivera-Pomar H Jackle (1996) ArticleTitleFrom gradients to stripes in Drosophila embryogenesis: filling in the gaps. Trends Genet 12 478–483 Occurrence Handle10.1016/0168-9525(96)10044-5 Occurrence Handle1:CAS:528:DyaK28XntVKnsbg%3D Occurrence Handle8973159

    Article  CAS  PubMed  Google Scholar 

  19. RF Ryan DC Schultz K Ayyanathan PB Singh JR Friedman et al. (1999) ArticleTitleKAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing. Mol Cell Biol 19 4366–4378 Occurrence Handle1:CAS:528:DyaK1MXjt1yisrk%3D Occurrence Handle10330177

    CAS  PubMed  Google Scholar 

  20. F Sanger S Niclen AR Coulson (1977) ArticleTitleDNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74 5463–5467 Occurrence Handle271968

    PubMed  Google Scholar 

  21. DC Schultz JR Friedman FJ 3rd Rauscher (2001) ArticleTitleTargeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev 15 428–443 Occurrence Handle10.1101/gad.869501 Occurrence Handle1:CAS:528:DC%2BD3MXhvVOju7Y%3D Occurrence Handle11230151

    Article  CAS  PubMed  Google Scholar 

  22. DC Schultz K Ayyanathan D Negorev GG Maul FJ 3rd Rauscher (2002) ArticleTitleSETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 16 919–932 Occurrence Handle10.1101/gad.973302 Occurrence Handle1:CAS:528:DC%2BD38Xjt1Gktb0%3D Occurrence Handle11959841

    Article  CAS  PubMed  Google Scholar 

  23. M Shannon J Kim L Ashworth E Branscomb L Stubbs (1998) ArticleTitleTandem zinc-finger gene families in mammals: insights and unanswered questions. DNA Seq 8 303–315 Occurrence Handle1:CAS:528:DyaK1cXltlylsrg%3D Occurrence Handle10993601

    CAS  PubMed  Google Scholar 

  24. JD Thompson DG Higgins TJ Gibson (1994) ArticleTitleCLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22 4673–4680 Occurrence Handle7984417

    PubMed  Google Scholar 

  25. C Underhill MS Qutob SP Yee J Torchia (2000) ArticleTitleA novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1. J Biol Chem 275 40463–40470 Occurrence Handle10.1074/jbc.M007864200 Occurrence Handle1:CAS:528:DC%2BD3MXhsFertQ%3D%3D Occurrence Handle11013263

    Article  CAS  PubMed  Google Scholar 

  26. JC Venter MD Adams EW Myers PW Li RJ Mural et al. (2001) ArticleTitleThe sequence of the human genome. Science 291 1304–1351 Occurrence Handle1:CAS:528:DC%2BD3MXhtlSgsbo%3D Occurrence Handle11181995

    CAS  PubMed  Google Scholar 

  27. H Vissing Wk Meyer L Aagaard N Tommerup HJ Thiesen (1995) ArticleTitleRepression of transcriptional activity by heterologous KRAB domains present in zinc finger proteins. FEBS Lett 369 153–157 Occurrence Handle10.1016/0014-5793(95)00728-R Occurrence Handle1:CAS:528:DyaK2MXnslyiu7s%3D Occurrence Handle7649249

    Article  CAS  PubMed  Google Scholar 

  28. RH Waterston K Lindblad-Toh E Birney J Rogers JF Abril et al. (2002) ArticleTitleInitial sequencing and comparative analysis of the mouse genome. Nature 420 520–562 Occurrence Handle10.1038/nature01262 Occurrence Handle12466850

    Article  PubMed  Google Scholar 

  29. BJ Westman JP Mackay D Gell (2002) ArticleTitleIkaros: a key regulator of haematopoiesis. Int J Biochem Cell Biol 34 1304–1307 Occurrence Handle10.1016/S1357-2725(02)00070-5 Occurrence Handle1:CAS:528:DC%2BD38XlsVOms7g%3D Occurrence Handle12127581

    Article  CAS  PubMed  Google Scholar 

  30. R Witzgall E O’Leary A Leaf D Onaldi JV Bonventre (1994) ArticleTitleThe Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc Natl Acad Sci USA 91 4514–4518 Occurrence Handle1:CAS:528:DyaK2cXkt1ynu74%3D Occurrence Handle8183940

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Patrik Johansson (Uppsala University) for introducing us to JPred and NPS@. This work was supported by a grant from the European Commission (BIOMED2).

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Correspondence to Magnus Åbrink.

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Looman, C., Hellman, L. & Åbrink, M. A novel Krüppel-associated box identified in a panel of mammalian zinc finger proteins . Mamm Genome 15, 35–40 (2004). https://doi.org/10.1007/s00335-003-3022-0

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