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Review
. 2003;4(10):231.
doi: 10.1186/gb-2003-4-10-231. Epub 2003 Sep 23.

KRAB-containing zinc-finger repressor proteins

Raul Urrutia  1
Affiliations
Review

KRAB-containing zinc-finger repressor proteins

Raul Urrutia. Genome Biol. 2003.

Abstract

The largest family of zinc-finger transcription factors comprises those containing the Krüppel-associated box (or KRAB domain), which are present only in tetrapod vertebrates. Many genes encoding KRAB-containing proteins are arranged in clusters in the human genome, with one cluster close to chromosome 9ql3 and others in centromeric and telomeric regions of other chromosomes, but other genes occur individually throughout the genome. The KRAB domain, which is found in the amino-terminal region of the proteins, behaves as a transcriptional repressor domain by binding to corepressor proteins, whereas the C2H2 zinc-finger motifs bind DNA. The functions currently proposed for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II, and III promoters and binding and splicing of RNA. Members of the family are involved in maintenance of the nucleolus, cell differentiation, cell proliferation, apoptosis, and neoplastic transformation.

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Figures

Figure 1
Figure 1
Primary structures of typical KRAB-containing zinc-finger proteins, illustrating the range of domains they contain. Note that the number of zinc fingers among proteins in the family is very variable, ranging from 4 to over 34; only 8 are shown in each structure here, for simplicity. The KRAB domain consists of the A and B boxes; some proteins contain a variant called the b box. Some members of the family have a leucine-rich SCAN domain that allows homo- and hetero-dimerization with other SCAN-containing zinc-finger proteins. Several proteins have been found corresponding to each of the structures shown; they therefore probably represent distinct structural and functional subfamilies. N, amino terminus; C, carboxyl terminus.
Figure 2
Figure 2
Alignments of the conserved KRAB and SCAN domains. (a)The KRAB domain, including both the A box and the B box. The A box is longer and more conserved than the B box. (b) The SCAN domain. This domain is found in non-zinc-finger proteins and zinc-finger proteins; the sequences shown here are for SCAN domains of KRAB-containing zinc-finger proteins. Note that these domains have a degree of conservation similar to that of the KRAB A box. Identical residues are in black, similar residues in gray and different residues in lower case. All sequences start at the first amino-acid residue.
Figure 3
Figure 3
A current model for the complex formed by KRAB-containing proteins and other proteins. A KRAB-containing protein binds specifically to a gene promoter through its multiple zinc fingers. A trimeric Kap1 complex binds to the KRAB domain of the KRAB-containing protein and serves as a scaffold for recruitment of HP1, HDACs, and Setdb1, to form heterochromatin. Note that the figure does not include the SCAN domain because, apart from its ability to dimerize, the role of this domain remains poorly understood.
See this image and copyright information in PMC

References

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