A COMPASS in the voyage of defining the role of trithorax/MLL-containing complexes: linking leukemogensis to covalent modifications of chromatin

J Cell Biochem. 2005 Jun 1;95(3):429-36. doi: 10.1002/jcb.20421.


Chromosomal rearrangements and translocations play a major role in the pathogenesis of hematological malignancies. The trithorax-related mixed lineage leukemia (Mll) gene located on chromosome 11 is rearranged in a variety of aggressive human B and T lymphoid tumors as well as acute myeloid leukemia (AML) in both children and adults. It was first demonstrated for the yeast MLL homolog complex, Set1/COMPASS, and now for the MLL complex itself, that these complexes are histone methyltransferases capable of methylating the fourth lysine of histone H3. The post-translational modifications of histones by methylation have emerged as a key regulatory mechanism for both repression and activation of gene expression. Studies from several laboratories during the past few years have brought about a watershed of information defining the molecular machinery and factors involved in the recognition and modification of nucleosomal histones by methylation. In this review, we will discuss the recent findings regarding the molecular mechanism and consequences of histone modification by the MLL related protein containing complex COMPASS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Animals
  • Child
  • Chromatin / genetics
  • Chromatin / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia / genetics
  • Leukemia / metabolism*
  • Methylation
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Myeloid-Lymphoid Leukemia Protein
  • Proto-Oncogenes / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Chromatin
  • DNA-Binding Proteins
  • KMT2A protein, human
  • Multiprotein Complexes
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase