Abstract
Krüppel-associated box (KRAB) domain, present at the N terminus of mammalian C2H2 zinc finger proteins, binds KAP-1 (also named TIF1β or KRIP-1) that binds HP1α and SETDB1 (H3-K9 methyltransferase) as well as NuRD complexes (histone deacetylases). The KRAB domain tethers these binding proteins to a specific gene recognized by zinc fingers, resulting in a heterochromatin-associated, strong, long-term repression of the gene. The importance of such repression is reflected in the large number (two hundred ninety) of the KRAB zinc finger protein genes in the human genome and revealed by early stage-development failure of mouse embryos lacking the common corepressor, KAP-1 (TIF1β). Many reports have described KRAB zinc finger proteins that participate in a variety of cellular processes including development of organs and cell types such as heart, bone, sperm and hematopoietic cells. Some KRAB zinc finger proteins have an additional repression mechanism that is KRAB domain-independent and involves histone deactylases or NSD1 histone lysine methyltrasferase.
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References
Beckwith J, Zipser D, eds. The lactose operon. New York: Cold Spring Harbor Laboratory; 1970.
Ptashne M. A genetic switch. Cambridge: Blackwell Scientific Publications; 1986.
Wallrath LL. Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev 1998; 8(2):147–153.
Eissenberg JC, Elgin SC. The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev 2000; 10(2):204–210.
Henikoff S. Heterochromatin function in complex genomes. Biochim Biophys Acta 2000; 1470(1):O1–8.
Moosmann P, Georgiev O, Thiesen HJ et al. Silencing of RNA polymerases II and III-dependent transcription by the KRAB protein domain of KOX1, a Kruppel-type zinc finger factor. Biol Chem 1997; 378(7):669–677.
Howe M, Dimitri P, Berloco M et al. Cis-effects of heterochromatin on heterochromatic and euchromatic gene activity in Drosophila melanogaster. Genetics 1995; 140(3):1033–1045.
Margolin JF, Friedman JR, Meyer WK et al. Kruppel-associated boxes are potent transcriptional repression domains. Proc Natl Acad Sci USA 1994; 91(10):4509–4513.
Friedman JR, Fredericks WJ, Jensen DE et al. KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev 1996; 10(16):2067–2078.
Kim SS, Chen YM, O’Leary E et al. A 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 1996; 93(26):15299–15304.
Le Douarin B, Nielsen AL, Garnier JM et al. A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. Embo J 1996; 15(23):6701–6715.
Moosmann P, Georgiev O, Le Douarin B et al. Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Nucleic Acids Res 1996; 24(24):4859–4867.
Turner J, Crossley M. Mammalian Kruppel-like transcription factors: more than just a pretty finger. Trends Biochem Sci 1999; 24(6):236–240.
Bellefroid EJ, Poncelet DA, Lecocq PJ et al. The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci USA 1991; 88(9):3608–3612.
Rosati M, Marino M, Franze A et al. Members of the zinc finger protein gene family sharing a conserved N-terminal module. Nucleic Acids Res 1991; 19(20):5661–5667.
Rousseau-Merck MF, Koczan D, Legrand I et al. The KOX zinc finger genes: genome wide mapping of 368 ZNF PAC clones with zinc finger gene clusters predominantly in 23 chromosomal loci are confirmed by human sequences annotated in EnsEMBL. Cytogenet Genome Res 2002; 98(2–3):147–153.
Venter JC, Adams MD, Myers EW et al. The sequence of the human genome. Science 2001; 291(5507):1304–1351.
Mark C, Abrink M, Hellman L. Comparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes. DNA Cell Biol 1999; 18(5):381–396.
Looman C, Abrink M, Mark C et al. KRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers and complexity during evolution. Mol Biol Evol 2002; 19(12):2118–2130.
Looman C, Hellman L, Abrink M. A novel Kruppel-Associated Box identified in a panel of mammalian zinc finger proteins. Mamm Genome 2004; 15(1):35–40.
Tian Y, Breedveld GJ, Huang S et al. Characterization of ZNF333, a novel double KRAB domain containing zinc finger gene on human chromosome 19p13.1. Biochim Biophys Acta 2002; 1577(1):121–125.
Collins T, Stone JR, Williams AJ. All in the family: the BTB/POZ, KRAB, and SCAN domains. Mol Cell Biol 2001; 21(11):3609–3615.
Shannon M, Hamilton AT, Gordon L et al. Differential expansion of zinc-finger transcription factor loci in homologous human and mouse gene clusters. Genome Res 2003; 13(6A):1097–1110.
Dehal P, Predki P, Olsen AS et al. Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution. Science 2001; 293(5527):104–111.
Abrink M, Ortiz JA, Mark C et al. Conserved interaction between distinct Kruppel-associated box domains and the transcriptional intermediary factor 1 beta. Proc Natl Acad Sci USA 2001; 98(4):1422–1426.
Agata Y, Matsuda E, Shimizu A. Two novel Kruppel-associated box-containing zinc-finger proteins, KRAZ1 and KRAZ2, repress transcription through functional interaction with the corepressor KAP-1 (TIF1beta/KRIP-1). J Biol Chem 1999; 274:16412–16422.
Peng H, Begg GE, Schultz DC et al. Reconstitution of the KRAB-KAP-1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein-protein interactions. J Mol Biol 2000; 295(5):1139–1162.
Peng H, Begg GE, Harper SL et al. Biochemical analysis of the Kruppel-associated box (KRAB) transcriptional repression domain. J Biol Chem 2000; 275(24):18000–18010.
Cammas F, Mark M, Dolle P et al. Mice lacking the transcriptional corepressor TIF1beta are defective in early postimplantation development. Development 2000; 127(13):2955–2963.
Gemain-Desprez D, Bazinet M, Bouvier M et al. Oligomerization of transcriptional intermediary factor 1 regulators and interaction with ZNF74 nuclear matrix protein revealed by bioluminescence resonance energy transfer in living cells. J Biol Chem 2003; 278(25):22367–22373.
Nielsen AL, Ortiz JA, You J et al. Interaction 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 1999; 18(22):6385–6395.
Lechner MS, Begg GE, Speicher DW et al. Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential. Mol Cell Biol 2000; 20(17):6449–6465.
Schultz DC, Friedman JR, Rauscher FJ, 3rd. Targeting 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 2001; 15(4):428–443.
Schultz DC, Ayyanathan K, Negorev D et al. SETDB1: 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 2002; 16(8):919–932.
Ayyanathan K, Lechner MS, Bell P et al. Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev 2003; 17(15):1855–1869.
Cammas F, Oulad-Abdelghani M, Vonesch JL et al. Cell differentiation induces TIF1beta association with centromeric heterochromatin via an HP1 interaction. J Cell Sci 2002; 115 (Pt 17):3439–3448.
Zheng L, Pan H, Li S et al. Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1. Mol Cell 2000; 6(4):757–768.
Tan W, Zheng L, Lee WH et al. Functional dissection of transcription factor ZBRK1 reveals zinc fingers with dual roles in DNA-binding and BRCA1-dependent transcriptional repression. J Biol Chem 2004; 279(8):6576–6587.
Iuchi S. Three classes of C2H2 zinc finger proteins. Cell Mol Life Sci 2001; 58(4):625–635.
Nielsen AL, Jorgensen P, Lerouge T et al. Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif. Mol Cell Biol 2004; 24(12):5184–5196.
Yi Z, Li Y, Ma W et al. A novel KRAB zinc-finger protein, ZNF480, expresses in human heart and activates transcriptional activities of AP-1 and SRE. Biochem Biophys Res Commun 2004; 320(2):409–415.
Hering TM, Kazmi NH, Huynh TD et al. Characterization and chondrocyte differentiation stage-specific expression of KRAB zinc-finger protein gene ZNF470. Exp Cell Res 2004; 299(1):137–147.
Ganss B, Kobayashi H. The zinc finger transcription factor Zfp60 is a negative regulator of cartilage differentiation. J Bone Miner Res 2002; 17(12):2151–2160.
Jheon AH, Ganss B, Cheifetz S et al. Characterization of a novel KRAB/C2H2 zinc finger transcription factor involved in bone development. J Biol Chem 2001; 276(21):18282–18289.
Looman C, Mark C, Abrink M et al. MZF6D, a novel KRAB zinc-finger gene expressed exclusively in meiotic male germ cells. DNA Cell Biol 2003; 22(8):489–496.
Takashima H, Nishio H, Wakao H et al. Molecular cloning and characterization of a KRAB-containing zinc finger protein, ZNF317, and its isoforms. Biochem Biophys Res Commun 2001; 288(4):771–779.
Gebelein B, Urrutia R. Sequence-specific transcriptional repression by KS1, a multiple-zinc-finger-Kruppel-associated box protein. Mol Cell Biol 2001; 21(3):928–939.
Peng H, Zheng L, Lee WH et al. A common DNA-binding site for SZF1 and the BRCA1-associated zinc finger protein, ZBRK1. Cancer Res 2002; 62(13):3773–3781.
Iuchi S, Green H. Basonuclin, a zinc finger protein of keratinocytes and reproductive germ cells, binds to the rRNA gene promoter. Proc Natl Acad Sci USA 1999; 96(17):9628–9632.
Tseng H, Biegel JA, Brown RS. Basonuclin is associated with the ribosomal RNA genes on human keratinocyte mitotic chromosomes. J Cell Sci 1999; 112 Pt 18:3039–3047.
Roberts SG. Mechanisms of action of transcripton activation and repression domains. Cell Mol Life Sci 2000; 57:1149–1160.
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Iuchi, S. (2005). KRAB Zinc Finger Proteins: A Family of Repressors Mediating Heterochromatin-Associated Gene Silencing. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_21
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DOI: https://doi.org/10.1007/0-387-27421-9_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-48229-8
Online ISBN: 978-0-387-27421-8
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