Identification of SCAN dimerization domains in four gene families

Zinc-finger transcription factors are often accompanied by modular sequence motifs such as the Kruppel-associated box (KRAB) and the SCAN domain. The KRAB domain mediates transcriptional repression while the SCAN domain media tes selective protein dimerization. The hypoalphalipoproteinemia susceptibi lity gene ZNF202 encodes a SCAN box lad a KRAB domain followed by eight Cys (2)- His(2) zinc-finger motifs. In order to identify the existence of genes which encode proteins of structural homology to ZN F202, a mouse lambda li brary was screened with a human ZNF202 cDNA probe. The isolated cDNA clones represented three SCAN-domain-encoding gene families. We purified three no vel cDNAs that encode a SCAN-KRAB-(Cys(2)His(2)), domain alignment and one cDNA that encodes a SCAN-(Cys(2)His(2))(x) domain alignment. In addition, w e identified one cDNA sequence with a predicted protein sequence containing a KRAB-SCAN-KRAB-(Cys(2)-His(2))(x) domain alignment. Therefore, when comb ined with the recently discovered family of isolated SCAN -domain-encoding genes, four SCAN domain gene families can be distinguished. The consensus s equences for the murine SCAN and KRAB domains are highly conserved within t he mammalian phylogenetic tree which may be useful in elucidating the biolo gical function of these protein modules and the crucial residues responsibl e for their binding specificity. (C) 2001 Elsevier Science B.V. All rights reserved.