PHF2, M961 And ASH2L: CDNA Cloning And Identification Of Their Functions In Induced Differentiation Of Multipotential Leukemia Cell Lines

Genes of trithorax group (trxG) and Polycomb group (PcG) are required to maintain the correct patterns of Hox expression. The trxG and PcG act in a somewhat antagonistic manner to "lock-in" active and inactive states of Hox transcription, respectively. Both PcG and trxG proteins act to remodel chromatin altering the accessibility of DNA to factors required for gene transcription, in the natural state, trx-G/PcG proteins interact with each other to form multimeric higher-order structures, PcG proteins are involved in chromatin based gene silencing, while trxG proteins counteract the silencing effects of chromatin to maintain gene activity.A cysteine-rich motif was firstly noted in two Arabidopsis homeodomain proteins, HAT3.1 and HOX1A and was named as PHD (plant homeodomain) finger motif. This motif has a unique Cys4-His-Cys3 pattern, which is lightly conserved in evolution. Several Drosophila Pc-G protein e.g. polycomb-like (Pcl) and trx-G proteins e. g. TRX, ASH1 and ASH2 contain this motif. Research has also shown that PHD finger may be involved in chromatin-mediated transcriptional regulation.In Homo sapiens, some genes encoding PHD finger proteins have been identified through the analysis of chromosomal reciprocal translocation occurred in human leukemia cells. One is MLL (mixed-lineage leukemia, also called HRX, ALL or HTRX1) that is the human homologue of DrosophiLa trithorax (trx) gene and located at chromosome band 11q23. There are four PHD finger motifs in MLL protein. The target gene of MLL, ARP1...