Abstract
The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.
Highlights
The PR/SET domain family (PRDM) [PRDI-BF1 and RIZ1 homologous domain containing] gene family is a conserved subfamily of Kruppel-like zinc finger gene products, which share a conserved N-terminal PR (PRDI-BF1-RIZ1 homologous) domain, initially identified in two proteins: PRDI-BF1, currently named PRDM1 and RIZ1, called PRDM2 [1,2,3]
17 members are reported in humans even though two further members are considered as belonging to this family: zinc finger protein, friend of GATA1 (FOG) family member 1 (ZFPM1; FOG1) and zinc finger protein, FOG family member 2 (ZFPM2; FOG2) [2,4]
The PR domain is a subtype of the SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain that defines a large group of histone methyltransferases (HMTs), with some of them functioning as lysine methyltransferases (KMTs) [1,2,3]
Summary
The PRDM [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain containing] gene family is a conserved subfamily of Kruppel-like zinc finger gene products, which share a conserved N-terminal PR (PRDI-BF1-RIZ1 homologous) domain, initially identified in two proteins: PRDI-BF1, currently named PRDM1 and RIZ1, called PRDM2 [1,2,3]. PRDM proteins (PRDMs) lacking intrinsic activity are able to directly or indirectly recruit and interact with histone-modifying enzymes to positively or negatively regulate chromatin structure; these enzymes include HMTs, PRMT5 (protein methyltransferase 5), LSD1 (lysine specific demethylase 1, KDM1A), histone deacetylases (HDACs), and histone acetyltransferases (HATs) [1,2,3]. These molecular features imply their involvement in epigenetic regulation of gene expression [1,2,3]. We attempt to provide insights for the future use of PRDMs as diagnostic biomarkers or therapeutic targets, by directly affecting their intrinsic catalytic activities, or by indirectly affecting their regulated pathways
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