The SCAN Family: Characterization of ZNF174

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DESCRIPTION (provided by applicant): In a search for negative regulators of growth factor gene expression, our group cloned a new zinc finger transcription factor, which was designated ZNFI74. Analysis of the open reading frame revealed two types of conserved elements. The first of these structures were three consensus Cys2-His2 (C2H2) type zinc fingers, while the second was a novel extended motif which we designated the SCAN domain. The SCAN domain is a highly conserved 80 amino acid modular element that is found in a family of more than 50 human Cys2-His2 (C2H2) zinc finger proteins. Like the leucine zipper, the SCAN domain appears to control association of SCAN domain containing proteins into non-covalent, multisubunit complexes and may be the primary mechanism underlying partner choice in the oligomenzation of these zinc-finger transcription factors. An attractive possibility is that the domain generates combinatorial diversity within the SCAN family of proteins. Heterodimer formation could lead to novel DNA recognition properties or to different regulatory activities, thus expanding the repertoire of the family. Only a few of the SCAN family members have been characterized, but the initial findings suggest that these genes play roles in development and differentiation. Despite the number of members in this family, remarkably little is known about the domain itself or the functions of most of the proteins defined by the domain. To investigate this family, we propose three specific aims to define ZNF174 and characterize the SCAN domain. Specific Aim 1: To further characterize ZNF174, a founding member of the SCAN family; Specific Aim 2: To determine the proteins that interact with the ZNF174 SCAN domain; Specific Aim 3: To further characterize the ability of the ZNF 174 SCAN domain to inhibit DNA binding. Collectively, these studies should define this transcription factor and provide mechanistic insights into the large number of C2H2 type zinc finger proteins defined by the SCAN domain.