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NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress

ABSTRACT: It has become clear that DNA repair factors function not only in the maintenance of genomic integrity but also in active DNA demethylation and epigenetic gene regulation. This dual role raises the question if phenotypic abnormalities resulting from deficiency of DNA repair factors are due to DNA damage or impaired DNA demethylation. Here we investigate the bifunctional DNA glycosylases/lyases NEIL1 and NEIL2, which act in repair of oxidative lesions and in epigenetic demethylation.

ORGANISM(S): Mus musculus Xenopus laevis

PROVIDER: GSE130082 | GEO | 2019/09/16

REPOSITORIES: GEO

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Gene expression changes in Neil1 / Neil2 / Neil3 triple knockout mouse teratoma

Project description:The bifunctional DNA glycosylases / AP lyases NEIL1 and NEIL2 excise oxidative base damages, but can also enhance the steady-state turnover of thymine DNA glycosylase (TDG) during oxidative DNA demethylation (Schomacher et al. 2016; doi:10.1038/nsmb.3151). The dual role of NEILs in antagonizing base damages and promoting epigenetic gene reactivation prompted us to investigate the consequences of NEIL deficiency during embryonic stem cell differentiation. To account for any possible functional redundancy in the NEIL family, all three paralogs NEIL1, NEIL2 and NEIL3 were inactivated using CRISPR/Cas9 in mouse embryonic stem cells.

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Gene expression changes in Neil1, Neil2 and Apex1 single knockout mouse embryonic stem cells prior and during embryoid body differentiation

Project description:The bifunctional DNA glycosylases/AP lyases NEIL1 and NEIL2 excise oxidative base damages, but can also enhance the steady-state turnover of thymine DNA glycosylase (TDG) during oxidative DNA demethylation (Schomacher et al. 2016; doi:10.1038/nsmb.3151) probably due to their AP lyase activity during base excision repair (BER). The dual role of NEILs in antagonizing base damages and promoting epigenetic gene reactivation prompted us to investigate the consequences of Neil-deficiency during embryonic stem cell differentiation. For comparison stem cells deficient for Apex1, the bona fide AP endonuclease during BER, were analysed in parallel.

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Genome-wide analysis of gene expression in postnatal hippocampus of Neil1 and Neil2-deficient mice after hypoxia ischemia (HI)

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Genome-wide bisulfite sequencing (GWBS) and RNA-seq in hippocampus of Neil1- and Neil2 deficient mice

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NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress

Project description:NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress

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spatial transcriptome

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Gene expression changes in Neil1 / Neil2 / Neil3 triple knockout mouse teratoma

Project description:Gene expression changes in Neil1 / Neil2 / Neil3 triple knockout mouse teratoma

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