Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)

Cells. 2020 Dec 4;9(12):2603. doi: 10.3390/cells9122603.

Abstract

PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) (PR) homologous domain containing (PRDM) transcription factors are expressed in neuronal and stem cell systems, and they exert multiple functions in a spatiotemporal manner. Therefore, it is believed that PRDM factors cooperate with a number of protein partners to regulate a critical set of genes required for maintenance of stem cell self-renewal and differentiation through genetic and epigenetic mechanisms. In this review, we summarize recent findings about the expression of PRDM factors and function in stem cell and neuronal systems with a focus on cofactor-dependent regulation of PRDM3/16 and FOG1/2. We put special attention on summarizing the effects of the PRDM proteins interaction with chromatin modulators (NuRD complex and CtBPs) on the stem cell characteristic and neuronal differentiation. Although PRDM factors are known to possess intrinsic enzyme activity, our literature analysis suggests that cofactor-dependent regulation of PRDM3/16 and FOG1/2 is also one of the important mechanisms to orchestrate bidirectional target gene regulation. Therefore, determining stem cell and neuronal-specific cofactors will help better understanding of PRDM3/16 and FOG1/2-controlled stem cell maintenance and neuronal differentiation. Finally, we discuss the clinical aspect of these PRDM factors in different diseases including cancer. Overall, this review will help further sharpen our knowledge of the function of the PRDM3/16 and FOG1/2 with hopes to open new research fields related to these factors in stem cell biology and neuroscience.

Keywords: CtBP; FOG; NuRD; PRDM; neurons; stem cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromatin / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • MDS1 and EVI1 Complex Locus Protein / metabolism*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Mice
  • Mutation
  • Neurons / metabolism*
  • Neurosciences
  • Nuclear Proteins / metabolism*
  • Positive Regulatory Domain I-Binding Factor 1 / metabolism*
  • Protein Domains
  • Risk
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / metabolism*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Nuclear Proteins
  • PRDM16 protein, human
  • Transcription Factors
  • ZFPM1 protein, human
  • ZFPM2 protein, human
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex