Genomic expansion and clustering of ZAD-containing C2H2 zinc-finger genes in Drosophila

Abstract

C2H2 zinc-finger proteins (ZFPs) constitute the largest family of nucleic acid binding factors in higher eukaryotes. In silico analysis identified a total of 326 putative ZFP genes in the Drosophila genome, corresponding to approximately 2.3% of the annotated genes. Approximately 29% of the Drosophila ZFPs are evolutionary conserved in humans and/or Caenorhabditis elegans. In addition, approximately 28% of the ZFPs contain an N-terminal zinc-finger-associated C4DM domain (ZAD) consisting of approximately 75 amino acid residues. The ZAD is restricted to ZFPs of dipteran and closely related insects. The evolutionary restriction, an expansion of ZAD-containing ZFP genes in the Drosophila genome and their clustering at few chromosomal sites are features reminiscent of vertebrate KRAB-ZFPs. ZADs are likely to represent protein-protein interaction domains. We propose that ZAD-containing ZFP genes participate in transcriptional regulation either directly or through site-specific modification and/or regulation of chromatin.

Figure 1

Multiple sequence alignment of a representative subset of 32 ZAD-containing ZFPs. Yellow boxes, invariant cysteine pairs; green characters, highly conserved arginine residues; red characters, conserved (>60%) hydrophobic amino acid residues. Blocks 1–4 are framed; r1–r3 denote the variable regions 1–3. Green arrows point to putative β-strands, red cylinders putative α-helical structures. The dashed arrow points to a weakly predicted β-strand (see Supplementary data for an alignment of the 91 Drosophila ZADs and a comparison with ZADs identified within the genome of A. gambiae).