2. Academic Validation
  3. KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions

KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions

  • J Mol Biol. 2024 Apr 1;436(7):168453. doi: 10.1016/j.jmb.2024.168453.
Hieu T Van 1,  Guojia Xie 2,  Peng Dong 3,  Zhe Liu 4,  Kai Ge 5
Affiliations

Affiliations

  • 1 Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 50, Room 4149, 50 South Dr, Bethesda, MD 20892, USA. Electronic address: [email protected].
  • 2 Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 50, Room 4149, 50 South Dr, Bethesda, MD 20892, USA. Electronic address: [email protected].
  • 3 Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: [email protected].
  • 4 Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: [email protected].
  • 5 Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 50, Room 4149, 50 South Dr, Bethesda, MD 20892, USA. Electronic address: [email protected].
PMID: 38266981 DOI: 10.1016/j.jmb.2024.168453
Abstract

Histone-lysine N-methyltransferase 2 (KMT2) methyltransferases are critical for gene regulation, cell differentiation, animal development, and human diseases. KMT2 biological roles are often attributed to their methyltransferase activities on lysine 4 of histone H3 (H3K4). However, recent data indicate that KMT2 proteins also possess non-enzymatic functions. In this review, we discuss the current understanding of KMT2 family, with a focus on their enzymatic activity-dependent and -independent functions. Six mammalian KMT2 proteins of three subgroups, KMT2A/B (MLL1/2), KMT2C/D (MLL3/4), and KMT2F/G (SETD1A/B or SET1A/B), have shared and distinct protein domains, catalytic substrates, genomic localizations, and associated complex subunits. Recent studies have revealed the importance of KMT2C/D in enhancer regulation, differentiation, development, tumor suppression and highlighted KMT2C/D enzymatic activity-dependent and -independent roles in mouse embryonic development and cell differentiation. Catalytic dependent and independent functions for KMT2A/B and KMT2F/G in gene regulation, differentiation, and development are less understood. Finally, we provide our perspectives and lay out future research directions that may help advance the investigation on enzymatic activity-dependent and -independent biological roles and working mechanisms of KMT2 methyltransferases.

Keywords

H3K4 methyltransferases; KMT2; MLL; gene regulation; organism development.

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