Arginine methyltransferases in normal and malignant hematopoiesis

Exp Hematol. 2016 Jun;44(6):435-41. doi: 10.1016/j.exphem.2016.03.009. Epub 2016 Mar 26.

Abstract

Arginine methylation is an abundant covalent modification that regulates diverse cellular processes, including transcription, translation, DNA repair, and RNA processing. The enzymes that catalyze these marks are known as the protein arginine methyltransferases (PRMTs), and they can generate asymmetric dimethyl arginine (type I arginine methyltransferases), symmetric dimethylarginine (type II arginine methyltransferases), or monomethyarginine (type III arginine methyltransferases). The PRMTs are capable of modifying diverse substrates, from histone components to specific nuclear and cytoplasmic proteins. Additionally, the PRMTs can orchestrate chromatin remodeling by blocking the docking of other epigenetic modifying enzymes or by recruiting them to specific gene loci. In the hematopoietic system, PRMTs can regulate cell behavior, including the critical balance between stem cell self-renewal and differentiation, in at least two critical ways, via (i) the covalent modification of transcription factors and (ii) the regulation of histone modifications at promoters critical to cell fate determination. Given these important functions, it is not surprising that these processes are altered in hematopoietic malignancies, such as acute myeloid leukemia, where they promote increased self-renewal and impair hematopoietic stem and progenitor cell differentiation.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Cells / metabolism
  • Cell Differentiation
  • Cell Self Renewal
  • DNA Repair
  • Gene Expression
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism*
  • Hematopoiesis* / genetics
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Methylation
  • Protein Isoforms
  • Protein-Arginine N-Methyltransferases / genetics*
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Signal Transduction

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Isoforms
  • PRMT2 protein, human
  • Protein-Arginine N-Methyltransferases