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

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 comprehe...

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Autores principales:	Basilia Acurzio, Ankit Verma, Alessia Polito, Carlo Giaccari, Francesco Cecere, Salvatore Fioriniello, Floriana Della Ragione, Annalisa Fico, Flavia Cerrato, Claudia Angelini, Robert Feil, Andrea Riccio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c8c1651a3bf4c37b51d4600ee824ba6
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spelling	oai:doaj.org-article:6c8c1651a3bf4c37b51d4600ee824ba62021-12-02T15:22:57ZZfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs10.1038/s41598-021-93297-32045-2322https://doaj.org/article/6c8c1651a3bf4c37b51d4600ee824ba62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93297-3https://doaj.org/toc/2045-2322Abstract 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.Basilia AcurzioAnkit VermaAlessia PolitoCarlo GiaccariFrancesco CecereSalvatore FiorinielloFloriana Della RagioneAnnalisa FicoFlavia CerratoClaudia AngeliniRobert FeilAndrea RiccioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Basilia Acurzio Ankit Verma Alessia Polito Carlo Giaccari Francesco Cecere Salvatore Fioriniello Floriana Della Ragione Annalisa Fico Flavia Cerrato Claudia Angelini Robert Feil Andrea Riccio Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
description	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.
format	article
author	Basilia Acurzio Ankit Verma Alessia Polito Carlo Giaccari Francesco Cecere Salvatore Fioriniello Floriana Della Ragione Annalisa Fico Flavia Cerrato Claudia Angelini Robert Feil Andrea Riccio
author_facet	Basilia Acurzio Ankit Verma Alessia Polito Carlo Giaccari Francesco Cecere Salvatore Fioriniello Floriana Della Ragione Annalisa Fico Flavia Cerrato Claudia Angelini Robert Feil Andrea Riccio
author_sort	Basilia Acurzio
title	Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
title_short	Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
title_full	Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
title_fullStr	Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
title_full_unstemmed	Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs
title_sort	zfp57 inactivation illustrates the role of icr methylation in imprinted gene expression during neural differentiation of mouse escs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6c8c1651a3bf4c37b51d4600ee824ba6
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Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs

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