• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Aug 11, 1994; 22(15): 2908–2914.
PMCID: PMC310254

Repression of transcriptional activity at a distance by the evolutionarily conserved KRAB domain present in a subfamily of zinc finger proteins.

Abstract

Sub-families of related zinc finger protein genes have been defined on the basis of evolutionarily conserved structural features found outside the C2-H2 finger repeats. Such elements include the FAX domain found in a large number of Xenopus ZFPs, the evolutionarily conserved KRAB (Krüppel-associated box) and the ZiN (zinc finger N-terminal) domains. Here we describe a new evolutionarily conserved motif within zinc finger proteins which we have named the leucine rich region (LeR). Since conserved modules in regulatory proteins may specify properties relevant to their action we have determined the functional capabilities of LeR and the KRAB domains in the regulation of gene transcription by fusing relevant regions to a heterologous DNA-binding domain (GAL4 DNA-binding domain). We found that the KRAB-A domain tethered to RNA polymerase II promoters by a GAL4 DNA-binding domain actively represses transcription in a distance-independent manner. KRAB-mediated repression is dependent on the dose of the GAL4-KRAB-A fusion protein and on the presence of GAL4 binding sites on the DNA. Conversely, the LeR domain did not modulate significantly the transcription. Our results indicate that the KRAB domain present in the non-finger region of many ZFP genes quenches transcription possibly due to specific protein-protein interactions between the KRAB-A domain and components of the proximal transcriptional apparatus.

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.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lee MS, Gippert GP, Soman KV, Case DA, Wright PE. Three-dimensional solution structure of a single zinc finger DNA-binding domain. Science. 1989 Aug 11;245(4918):635–637. [PubMed]
  • Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. [PMC free article] [PubMed]
  • Brown RS, Sander C, Argos P. The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett. 1985 Jul 8;186(2):271–274. [PubMed]
  • Párraga G, Horvath SJ, Eisen A, Taylor WE, Hood L, Young ET, Klevit RE. Zinc-dependent structure of a single-finger domain of yeast ADR1. Science. 1988 Sep 16;241(4872):1489–1492. [PubMed]
  • Bellefroid EJ, Lecocq PJ, Benhida A, Poncelet DA, Belayew A, Martial JA. The human genome contains hundreds of genes coding for finger proteins of the Krüppel type. DNA. 1989 Jul-Aug;8(6):377–387. [PubMed]
  • el-Baradi T, Pieler T. Zinc finger proteins: what we know and what we would like to know. Mech Dev. 1991 Nov;35(3):155–169. [PubMed]
  • Schuh R, Aicher W, Gaul U, Côté S, Preiss A, Maier D, Seifert E, Nauber U, Schröder C, Kemler R, et al. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Krüppel, a Drosophila segmentation gene. Cell. 1986 Dec 26;47(6):1025–1032. [PubMed]
  • Knöchel W, Pöting A, Köster M, el Baradi T, Nietfeld W, Bouwmeester T, Pieler T. Evolutionary conserved modules associated with zinc fingers in Xenopus laevis. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6097–6100. [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]
  • Rosati M, Marino M, Franzè A, Tramontano A, Grimaldi G. Members of the zinc finger protein gene family sharing a conserved N-terminal module. Nucleic Acids Res. 1991 Oct 25;19(20):5661–5667. [PMC free article] [PubMed]
  • Numoto M, Niwa O, Kaplan J, Wong KK, Merrell K, Kamiya K, Yanagihara K, Calame K. Transcriptional repressor ZF5 identifies a new conserved domain in zinc finger proteins. Nucleic Acids Res. 1993 Aug 11;21(16):3767–3775. [PMC free article] [PubMed]
  • Pengue G, Calabrò V, Cannada-Bartoli P, De Luca P, Esposito T, Taillon-Miller P, LaForgia S, Druck T, Huebner K, D'Urso M, et al. YAC-assisted cloning of transcribed sequences from the human chromosome 3p21 region. Hum Mol Genet. 1993 Jun;2(6):791–796. [PubMed]
  • Sadowski I, Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. [PMC free article] [PubMed]
  • Ursini MV, Lettieri T, Braddock M, Martini G. Enhanced activity of human G6PD promoter transfected in HeLa cells producing high levels of HIV-1 Tat. Virology. 1993 Sep;196(1):338–343. [PubMed]
  • Lillie JW, Green MR. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. [PubMed]
  • Carey M, Lin YS, Green MR, Ptashne M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature. 1990 May 24;345(6273):361–364. [PubMed]
  • Attar RM, Gilman MZ. Expression cloning of a novel zinc finger protein that binds to the c-fos serum response element. Mol Cell Biol. 1992 May;12(5):2432–2443. [PMC free article] [PubMed]
  • Denny P, Ashworth A. A zinc finger protein-encoding gene expressed in the post-meiotic phase of spermatogenesis. Gene. 1991 Oct 15;106(2):221–227. [PubMed]
  • Chowdhury K, Goulding M, Walther C, Imai K, Fickenscher H. The ubiquitous transactivator Zfp-38 is upregulated during spermatogenesis with differential transcription. Mech Dev. 1992 Dec;39(3):129–142. [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]
  • 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]
  • Descombes P, Schibler U. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell. 1991 Nov 1;67(3):569–579. [PubMed]
  • Foulkes NS, Sassone-Corsi P. More is better: activators and repressors from the same gene. Cell. 1992 Feb 7;68(3):411–414. [PubMed]
  • Molina CA, Foulkes NS, Lalli E, Sassone-Corsi P. Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell. 1993 Dec 3;75(5):875–886. [PubMed]
  • Stehle JH, Foulkes NS, Molina CA, Simonneaux V, Pévet P, Sassone-Corsi P. Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland. Nature. 1993 Sep 23;365(6444):314–320. [PubMed]
  • Roman C, Cohn L, Calame K. A dominant negative form of transcription activator mTFE3 created by differential splicing. Science. 1991 Oct 4;254(5028):94–97. [PubMed]
  • Mumberg D, Lucibello FC, Schuermann M, Müller R. Alternative splicing of fosB transcripts results in differentially expressed mRNAs encoding functionally antagonistic proteins. Genes Dev. 1991 Jul;5(7):1212–1223. [PubMed]
  • Nakabeppu Y, Nathans D. A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity. Cell. 1991 Feb 22;64(4):751–759. [PubMed]
  • Levine M, Manley JL. Transcriptional repression of eukaryotic promoters. Cell. 1989 Nov 3;59(3):405–408. [PubMed]
  • Cowell IG. Repression versus activation in the control of gene transcription. Trends Biochem Sci. 1994 Jan;19(1):38–42. [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]
  • Yew PR, Liu X, Berk AJ. Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev. 1994 Jan;8(2):190–202. [PubMed]
  • Roth SY, Dean A, Simpson RT. Yeast alpha 2 repressor positions nucleosomes in TRP1/ARS1 chromatin. Mol Cell Biol. 1990 May;10(5):2247–2260. [PMC free article] [PubMed]
  • Licht JD, Ro M, English MA, Grossel M, Hansen U. Selective repression of transcriptional activators at a distance by the Drosophila Krüppel protein. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11361–11365. [PMC free article] [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...