SET/MLL family proteins in hematopoiesis and leukemia

Int J Hematol. 2017 Jan;105(1):7-16. doi: 10.1007/s12185-016-2118-8. Epub 2016 Oct 31.

Abstract

Accumulating recent evidence supports the notion that many enzymes that modify histones are fundamental players in normal hematopoiesis as well as hematologic malignancies, and represent an important new class of drug targets. Histone H3 lysine 4 (H3K4) methylation plays several distinct roles in gene expression and is modulated by specific methyltransferases and demethylases. Recent progress has been made clarifying the unique biological roles of the enzymes that carry out H3K4 methylation, yet a detailed understanding of H3K4 methylation states in various genomic contexts and the diverse functions of the enzymes that perform these methylation events is incomplete, but developing rapidly. In this review, we summarize and discuss the general mechanisms of H3K4 methylation, and how the six main enzymes from the SET/MLL family (responsible for H3K4me1/me2/me3) function in hematopoiesis and in hematologic malignancies.

Keywords: AML; H3K4 methylation; Histone methyltransferase; Leukemia; MLL1; MLL2; Wbp7.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins
  • Hematopoiesis*
  • Histone Chaperones / metabolism*
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism*
  • Humans
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Methylation
  • Myeloid-Lymphoid Leukemia Protein / metabolism*
  • Protein Interaction Maps
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • Histones
  • KMT2A protein, human
  • SET protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase