Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs - Archive ouverte HAL Access content directly
Journal Articles Scientific Reports Year : 2021

Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs

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Basilia Acurzio
  • Function : Author
Ankit Verma
  • Function : Author
Alessia Polito
  • Function : Author
Carlo Giaccari
  • Function : Author
Francesco Cecere
  • Function : Author
Salvatore Fioriniello
  • Function : Author
Floriana Della Ragione
  • Function : Author
Annalisa Fico
  • Function : Author
Flavia Cerrato
  • Function : Author
Claudia Angelini
  • Function : Author
Andrea Riccio
  • Function : Author

Abstract

ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57 -/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57 -mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.
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hal-03434515 , version 1 (18-11-2021)

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Basilia Acurzio, Ankit Verma, Alessia Polito, Carlo Giaccari, Francesco Cecere, et al.. Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs. Scientific Reports, 2021, 11 (1), ⟨10.1038/s41598-021-93297-3⟩. ⟨hal-03434515⟩
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