MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia.
Proteins encoded by Polycomb and Trithorax-group (Pc-G and Trx-G) genes regulate developmental fates by maintaining or repressing HOX gene expression, respectively. In a search for candidate myeloid leukemia tumor suppressor genes from a approximately 2.5 Mb commonly-deleted segment within chromosome band 7q22, we identified a novel human Trithorax (Trx) family member named MLL5. Trx-G genes encode proteins that modulate transcriptional programs through protein-protein interactions that are mediated by PHD and SET domains, and by binding to DNA via A-T hooks and methyltransferase homology motifs. MLL5 is a homolog of the Drosophila gene CG9007; it encodes a 6.5 kb mRNA that is expressed widely. MLL5 includes a SET domain and a single PHD finger, but lacks A-T hooks and methyltransferase homology domains that are found in MLL. The leukemia cell line RCV-ACV-A carries a heterozygous missense mutation within the PHD domain; however, no mutations within the MLL5 coding region were detected in primary leukemias. MLL5 is a novel mammalian Trx-G gene that might modulate transcription by protein association.
Emerling
Brooke M
BM
Department of Pediatrics and Comprehensive Cancer Center, University of California, San Francisco, California, CA 94143, USA.
Bonifas
Jeannette
J
Kratz
Christian P
CP
Donovan
Shane
S
Taylor
Brigit R
BR
Green
Eric D
ED
Le Beau
Michelle M
MM
Shannon
Kevin M
KM
D000595:Amino Acid Sequence; D000818:Animals; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D029721:Drosophila Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C460660:KMT2E protein, human; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D012313:RNA