The conserved PHD1-PHD2 domain of ZFP-1/AF10 is a discrete functional module essential for viability in Caenorhabditis elegans.
Plant homeodomain (PHD)-type zinc fingers play an important role in recognizing chromatin modifications and recruiting regulatory proteins to specific genes. A specific module containing a conventional PHD finger followed by an extended PHD finger exists in the mammalian AF10 protein, among a few others. AF10 has mostly been studied in the context of the leukemic MLL-AF10 fusion protein, which lacks the N-terminal PHD fingers of AF10. Although this domain of AF10 is the most conserved region of the protein, its biological significance has not been elucidated. In this study, we used genetic and biochemical approaches to examine the PHD1-PHD2 region of the Caenorhabditis elegans ortholog of AF10, zinc finger protein 1 (ZFP-1). We demonstrate that the PHD1-PHD2 region is essential for viability and that the first PHD finger contributes to the preferred binding of PHD1-PHD2 to lysine 4-methylated histone H3 tails. Moreover, we show that ZFP-1 localization peaks overlap with H3K4 methylation-enriched promoters of actively expressed genes genomewide and that H3K4 methylation is important for ZFP-1 localization to promoters in the embryo. We predict that the essential biological role of the PHD1-PHD2 module of ZFP-1/AF10 is connected to the regulation of actively expressed genes during early development.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T3 T4 T5 T6 T7 T8 T9
GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-N CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-Y GENE-Y
PHD finger PHD finger AF10 AF10 MLL AF10 N-terminal PHD fingers AF10 AF10 PHD1-PHD2 zinc AF10 zinc finger protein 1 ZFP-1 PHD1-PHD2 PHD finger PHD1-PHD2 ZFP-1 PHD1-PHD2 domain ZFP-1 AF10 N zinc lysine Plant homeodomain (PHD)-type zinc fingers ZFP-1 PHD1-PHD2 ZFP-1 AF10