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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.
Highlights
PRDI-BF1 and RIZ1 (PR) homologous-domain-containing (PRDM) transcription factors have received considerable attention recently due to their importance in regulating the development and function of various tissues and organ systems
DNA demethylation status in the embryonic stem cells via TET proteins [54]. These results suggest that the demethylation status observed during the induction of pluripotency is controlled by PRDM14
FOG2 was found exclusively in postmitotic neurons in the cortex as well as in the thalamic reticular nucleus, the hippocampus, the amygdala and the hypothalamus. These findings strongly suggest that FOG2 plays a role as a transcriptional regulator during the final stage of neuronal maturation [93]
Summary
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 have received considerable attention recently due to their importance in regulating the development and function of various tissues and organ systems. The PRDM protein family is a group of 19 poorly studied factors that are involved in a wide range of cellular processes [1,2,3,4]. (suppressor of variegation 3–9, enhancer of zeste and trithorax) domain, which possesses histone lysine methyltransferase (HMT) activity [5]. Depending on the cellular or tissue context, PRDM proteins mediate either transcriptional repression or activation. PRDM1, PRDM5, PRDM6 and PRDM12 are known to interact with G9a HMT and repress gene expression through methylation of H3 lysine 9 [6,7,8,12,22]. Expression level predicts embryonic stem cells and progenitors’ fate (mechanism partially dependent on PRL family members)
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