MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia

Oncogene. 2002 Jul 18;21(31):4849-54. doi: 10.1038/sj.onc.1205615.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosome Deletion
  • Chromosomes, Human, Pair 7*
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukemia, Myeloid / genetics*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA / biosynthesis
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Drosophila Proteins
  • KMT2E protein, human
  • Transcription Factors
  • Trl protein, Drosophila
  • RNA