• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. May 10, 1994; 91(10): 4509–4513.
PMCID: PMC43815

Krüppel-associated boxes are potent transcriptional repression domains.

Abstract

The Krüppel-associated box (KRAB) is a highly conserved, 75-aa region containing two predicted amphipathic alpha-helices. The KRAB domain is present in the amino-terminal regions of more than one-third of all Krüppel-class Cys2His2 zinc finger proteins and is conserved from yeast to man; however, its function is unknown. Here it is shown that the KRAB domain functions as a DNA binding-dependent transcriptional repressor when fused to a heterologous DNA-binding domain from the yeast GAL4 protein. A 45-aa segment containing one of the predicted KRAB amphipathic helices was necessary and sufficient for repression. Amino acid substitutions in the predicted helix abolished the repression function. These results assign a function, transcriptional repression, to the highly conserved KRAB box and define a minimal repression domain which may aid in identifying mechanisms of repression.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pabo CO, Sauer RT. Transcription factors: structural families and principles of DNA recognition. Annu Rev Biochem. 1992;61:1053–1095. [PubMed]
  • Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. [PubMed]
  • Johnson PF, McKnight SL. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. [PubMed]
  • Stringer KF, Ingles CJ, Greenblatt J. Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990 Jun 28;345(6278):783–786. [PubMed]
  • Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L. Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell. 1990 Jun 29;61(7):1199–1208. [PubMed]
  • Berger SL, Piña B, Silverman N, Marcus GA, Agapite J, Regier JL, Triezenberg SJ, Guarente L. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell. 1992 Jul 24;70(2):251–265. [PubMed]
  • Cress WD, Triezenberg SJ. Critical structural elements of the VP16 transcriptional activation domain. Science. 1991 Jan 4;251(4989):87–90. [PubMed]
  • Leuther KK, Salmeron JM, Johnston SA. Genetic evidence that an activation domain of GAL4 does not require acidity and may form a beta sheet. Cell. 1993 Feb 26;72(4):575–585. [PubMed]
  • Levine M, Manley JL. Transcriptional repression of eukaryotic promoters. Cell. 1989 Nov 3;59(3):405–408. [PubMed]
  • Renkawitz R. Transcriptional repression in eukaryotes. Trends Genet. 1990 Jun;6(6):192–197. [PubMed]
  • Cowell IG, Skinner A, Hurst HC. Transcriptional repression by a novel member of the bZIP family of transcription factors. Mol Cell Biol. 1992 Jul;12(7):3070–3077. [PMC free article] [PubMed]
  • Madden SL, Cook DM, Morris JF, Gashler A, Sukhatme VP, Rauscher FJ., 3rd Transcriptional repression mediated by the WT1 Wilms tumor gene product. Science. 1991 Sep 27;253(5027):1550–1553. [PubMed]
  • Madden SL, Cook DM, Rauscher FJ., 3rd A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. Oncogene. 1993 Jul;8(7):1713–1720. [PubMed]
  • Licht JD, Grossel MJ, Figge J, Hansen UM. Drosophila Krüppel protein is a transcriptional repressor. Nature. 1990 Jul 5;346(6279):76–79. [PubMed]
  • Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. [PubMed]
  • Han K, Manley JL. Functional domains of the Drosophila Engrailed protein. EMBO J. 1993 Jul;12(7):2723–2733. [PMC free article] [PubMed]
  • Gashler AL, Swaminathan S, Sukhatme VP. A novel repression module, an extensive activation domain, and a bipartite nuclear localization signal defined in the immediate-early transcription factor Egr-1. Mol Cell Biol. 1993 Aug;13(8):4556–4571. [PMC free article] [PubMed]
  • Saha S, Brickman JM, Lehming N, Ptashne M. New eukaryotic transcriptional repressors. Nature. 1993 Jun 17;363(6430):648–652. [PubMed]
  • Keleher CA, Goutte C, Johnson AD. The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein. Cell. 1988 Jun 17;53(6):927–936. [PubMed]
  • Keleher CA, Redd MJ, Schultz J, Carlson M, Johnson AD. Ssn6-Tup1 is a general repressor of transcription in yeast. Cell. 1992 Feb 21;68(4):709–719. [PubMed]
  • Shimizu M, Roth SY, Szent-Gyorgyi C, Simpson RT. Nucleosomes are positioned with base pair precision adjacent to the alpha 2 operator in Saccharomyces cerevisiae. EMBO J. 1991 Oct;10(10):3033–3041. [PMC free article] [PubMed]
  • Roth SY, Shimizu M, Johnson L, Grunstein M, Simpson RT. Stable nucleosome positioning and complete repression by the yeast alpha 2 repressor are disrupted by amino-terminal mutations in histone H4. Genes Dev. 1992 Mar;6(3):411–425. [PubMed]
  • Thiesen HJ. Multiple genes encoding zinc finger domains are expressed in human T cells. New Biol. 1990 Apr;2(4):363–374. [PubMed]
  • Tommerup N, Aagaard L, Lund CL, Boel E, Baxendale S, Bates GP, Lehrach H, Vissing H. A zinc-finger gene ZNF141 mapping at 4p16.3/D4S90 is a candidate gene for the Wolf-Hirschhorn (4p-) syndrome. Hum Mol Genet. 1993 Oct;2(10):1571–1575. [PubMed]
  • Lania L, Donti E, Pannuti A, Pascucci A, Pengue G, Feliciello I, La Mantia G, Lanfrancone L, Pelicci PG. cDNA isolation, expression analysis, and chromosomal localization of two human zinc finger genes. Genomics. 1990 Feb;6(2):333–340. [PubMed]
  • Lovering R, Trowsdale J. A gene encoding 22 highly related zinc fingers is expressed in lymphoid cell lines. Nucleic Acids Res. 1991 Jun 11;19(11):2921–2928. [PMC free article] [PubMed]
  • Constantinou-Deltas CD, Gilbert J, Bartlett RJ, Herbstreith M, Roses AD, Lee JE. The identification and characterization of KRAB-domain-containing zinc finger proteins. Genomics. 1992 Mar;12(3):581–589. [PubMed]
  • Bellefroid EJ, Marine JC, Ried T, Lecocq PJ, Rivière M, Amemiya C, Poncelet DA, Coulie PG, de Jong P, Szpirer C, et al. Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. EMBO J. 1993 Apr;12(4):1363–1374. [PMC free article] [PubMed]
  • Bellefroid EJ, Poncelet DA, Lecocq PJ, Revelant O, Martial JA. The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3608–3612. [PMC free article] [PubMed]
  • Sadowski I, Bell B, Broad P, Hollis M. GAL4 fusion vectors for expression in yeast or mammalian cells. Gene. 1992 Sep 1;118(1):137–141. [PubMed]
  • Ma J, Ptashne M. Deletion analysis of GAL4 defines two transcriptional activating segments. Cell. 1987 Mar 13;48(5):847–853. [PubMed]
  • Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. [PubMed]
  • Lillie JW, Green MR. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. [PubMed]
  • Morris JF, Madden SL, Tournay OE, Cook DM, Sukhatme VP, Rauscher FJ., 3rd Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus. Oncogene. 1991 Dec;6(12):2339–2348. [PubMed]
  • Spaete RR, Mocarski ES. Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J Virol. 1985 Oct;56(1):135–143. [PMC free article] [PubMed]
  • Witzgall R, O'Leary E, Gessner R, Ouellette AJ, Bonventre JV. Kid-1, a putative renal transcription factor: regulation during ontogeny and in response to ischemia and toxic injury. Mol Cell Biol. 1993 Mar;13(3):1933–1942. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Conserved Domains
    Conserved Domains
    Link to related CDD entry
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...