Krüppel-associated Boxes Are Potent Transcriptional Repression Domains

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 May 10

PMID 8183939

Citations 237

Authors

J F Margolin

J R Friedman

W K Meyer

H Vissing

H J Thiesen

F J Rauscher 3rd

Affiliations

Soon will be listed here.

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.

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References

Leuther K, Salmeron J, Johnston S . Genetic evidence that an activation domain of GAL4 does not require acidity and may form a beta sheet. Cell. 1993; 72(4):575-85. DOI: 10.1016/0092-8674(93)90076-3. View

Sadowski I, Bell B, Broad P, Hollis M . GAL4 fusion vectors for expression in yeast or mammalian cells. Gene. 1992; 118(1):137-41. DOI: 10.1016/0378-1119(92)90261-m. View

Bellefroid E, Marine J, Ried T, Lecocq P, Riviere M, Amemiya C . Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. EMBO J. 1993; 12(4):1363-74. PMC: 413348. DOI: 10.1002/j.1460-2075.1993.tb05781.x. View

Saha S, Brickman J, Lehming N, Ptashne M . New eukaryotic transcriptional repressors. Nature. 1993; 363(6430):648-52. DOI: 10.1038/363648a0. View

Madden S, Cook D, Rauscher 3rd F . A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. Oncogene. 1993; 8(7):1713-20. View

Han K, Manley J . Functional domains of the Drosophila Engrailed protein. EMBO J. 1993; 12(7):2723-33. PMC: 413523. DOI: 10.1002/j.1460-2075.1993.tb05934.x. View

Gashler A, Swaminathan S, Sukhatme V . 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; 13(8):4556-71. PMC: 360074. DOI: 10.1128/mcb.13.8.4556-4571.1993. View

Tommerup N, Aagaard L, Lund C, Boel E, Baxendale S, Bates G . A zinc-finger gene ZNF141 mapping at 4p16.3/D4S90 is a candidate gene for the Wolf-Hirschhorn (4p-) syndrome. Hum Mol Genet. 1993; 2(10):1571-5. DOI: 10.1093/hmg/2.10.1571. View

Spaete R, Mocarski E . Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J Virol. 1985; 56(1):135-43. PMC: 252498. DOI: 10.1128/JVI.56.1.135-143.1985. View

10.

Ma J, Ptashne M . Deletion analysis of GAL4 defines two transcriptional activating segments. Cell. 1987; 48(5):847-53. DOI: 10.1016/0092-8674(87)90081-x. View

11.

Keleher C, Goutte C, Johnson A . The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein. Cell. 1988; 53(6):927-36. DOI: 10.1016/s0092-8674(88)90449-7. View

12.

Lillie J, Green M . Transcription activation by the adenovirus E1a protein. Nature. 1989; 338(6210):39-44. DOI: 10.1038/338039a0. View

13.

Ho S, Hunt H, Horton R, Pullen J, Pease L . Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989; 77(1):51-9. DOI: 10.1016/0378-1119(89)90358-2. View

14.

Mitchell P, Tjian R . Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989; 245(4916):371-8. DOI: 10.1126/science.2667136. View

15.

Johnson P, McKnight S . Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989; 58:799-839. DOI: 10.1146/annurev.bi.58.070189.004055. View

16.

Levine M, Manley J . Transcriptional repression of eukaryotic promoters. Cell. 1989; 59(3):405-8. DOI: 10.1016/0092-8674(89)90024-x. View

17.

Lania L, Donti E, Pannuti A, Pascucci A, Pengue G, Feliciello I . cDNA isolation, expression analysis, and chromosomal localization of two human zinc finger genes. Genomics. 1990; 6(2):333-40. DOI: 10.1016/0888-7543(90)90574-e. View

18.

Stringer K, Ingles C, GREENBLATT J . Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990; 345(6278):783-6. DOI: 10.1038/345783a0. View

19.

Berger S, Cress W, Cress A, Triezenberg S, Guarente L . Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell. 1990; 61(7):1199-208. DOI: 10.1016/0092-8674(90)90684-7. View

20.

Licht J, Grossel M, Figge J, Hansen U . Drosophila Krüppel protein is a transcriptional repressor. Nature. 1990; 346(6279):76-9. DOI: 10.1038/346076a0. View