Biology:Krüppel associated box

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Short description: Protein domain
Krüppel Associated Box
KRAB Domain.png
KRAB domain
Identifiers
SymbolKRAB
PfamPF01352
InterProIPR001909
SMARTSM00349
PROSITEPS50805
SCOP21v65 / SCOPe / SUPFAM

The Krüppel associated box (KRAB) domain is a category of transcriptional repression domains present in approximately 400 human zinc finger protein-based transcription factors (KRAB zinc finger proteins).[1] The KRAB domain typically consists of about 75 amino acid residues, while the minimal repression module is approximately 45 amino acid residues.[2] It is predicted to function through protein-protein interactions via two amphipathic helices. The most prominent interacting protein is called TRIM28 initially visualized as SMP1,[3] cloned as KAP1[4] and TIF1-beta.[5] Substitutions for the conserved residues abolish repression.

Over 10 independently encoded KRAB domains have been shown to be effective repressors of transcription, suggesting this activity to be a common property of the domain. KRAB domains can be fused with dCas9 CRISPR tools to form even stronger repressors.[6]

Evolution

The KRAB domain had initially been identified in 1988 as a periodic array of leucine residues separated by six amino acids 5’ to the zinc finger region of KOX1/ZNF10[7] coined heptad repeat of leucines (also known as a leucine zipper).[8] Later, this domain was named in association with the C2H2-Zinc finger proteins Krüppel associated box (KRAB).[9][10] The KRAB domain is confined to genomes from tetrapod organisms. The KRAB containing C2H2-ZNF genes constitute the largest sub-family of zinc finger genes. More than half of the C2H2-ZNF genes are associated with a KRAB domain in the human genome. They are more prone to clustering and are found in large clusters on the human genome.[11]

The KRAB domain presents one of the strongest repressors in the human genome.[2] Once the KRAB domain was fused to the tetracycline repressor (TetR), the TetR-KRAB fusion proteins were the first engineered drug-inducible repressor that worked in mammalian cells.[3]

Examples

Human genes encoding KRAB-ZFPs include KOX1/ZNF10, KOX8/ZNF708, ZNF43, ZNF184, ZNF91, HPF4, HTF10 and HTF34.

References

  1. ↑ "A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors". Genome Res. 16 (5): 669–77. May 2006. doi:10.1101/gr.4842106. PMID 16606702. 
  2. ↑ 2.0 2.1 "Krüppel-associated boxes are potent transcriptional repression domains". Proc. Natl. Acad. Sci. U.S.A. 91 (10): 4509–13. May 1994. doi:10.1073/pnas.91.10.4509. PMID 8183939. Bibcode: 1994PNAS...91.4509M. 
  3. ↑ 3.0 3.1 "Tetracycline-reversible silencing of eukaryotic promoters". Mol. Cell. Biol. 15 (4): 1907–14. April 1995. doi:10.1128/mcb.15.4.1907. PMID 7891684. 
  4. ↑ "KAP-1, a novel corepressor for the highly conserved KRAB repression domain". Genes Dev. 10 (16): 2067–78. August 1996. doi:10.1101/gad.10.16.2067. PMID 8769649. 
  5. ↑ "Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1". Nucleic Acids Res. 24 (24): 4859–67. December 1996. doi:10.1093/nar/24.24.4859. PMID 9016654. 
  6. ↑ Jensen, Trine I.; Mikkelsen, Nanna S.; Gao, Zongliang; Foßelteder, Johannes; Pabst, Gabriel; Axelgaard, Esben; Laustsen, Anders; König, Saskia et al. (2021-08-18). "Targeted regulation of transcription in primary cells using CRISPRa and CRISPRi". Genome Research 31 (11): 2120–2130. doi:10.1101/gr.275607.121. ISSN 1549-5469. PMID 34407984. 
  7. ↑ Basel Institute for Immunology (1988). Annual Report. Basel. p. 53. OCLC 1793356. https://books.google.com/books?id=-CJrAAAAMAAJ. 
  8. ↑ Thiesen, Hans-Jürgen (April 1990). "Multiple genes encoding zinc finger domains are expressed in human T cells". New Biol. 2 (4): 363–74. PMID 2288909. http://www.zinc-finger.com/zincfinger1.pdf. 
  9. ↑ "The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3608–12. May 1991. doi:10.1073/pnas.88.9.3608. PMID 2023909. Bibcode: 1991PNAS...88.3608B. 
  10. ↑ "Conserved KRAB protein domain identified upstream from the zinc finger region of Kox 8". Nucleic Acids Res. 19 (14): 3996. July 1991. doi:10.1093/nar/19.14.3996. PMID 1861988. 
  11. ↑ "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. 98 (2–3): 147–53. 2002. doi:10.1159/000069802. PMID 12697996. 

Further reading

  • "Biochemical analysis of the Kruppel-associated box (KRAB) transcriptional repression domain". J. Biol. Chem. 275 (24): 18000–10. June 2000. doi:10.1074/jbc.M001499200. PMID 10748030. 




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