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. 1994 May 10;91(10):4509–4513. doi: 10.1073/pnas.91.10.4509

Krüppel-associated boxes are potent transcriptional repression domains.

J F Margolin 1, J R Friedman 1, W K Meyer 1, H Vissing 1, H J Thiesen 1, F J Rauscher 3rd 1
PMCID: PMC43815  PMID: 8183939

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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