Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino-terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 translocations disrupt the HRX gene between these two motifs, and in a t(11;19)-carrying cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation.
Tkachuk
D C
DC
Department of Pathology, Stanford University School of Medicine, California 94305.
Kohler
S
S
Cleary
M L
ML
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D015533:Transcriptional Activation; D014178:Translocation, Genetic / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase