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Analysis of FOXO3 human targets in Huntington's disease neural stem cells

ABSTRACT: Analysis of FOXO3 human targets in Huntington's disease neural stem cells

PROVIDER: PRJNA432220 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6653260.fastq.gz	Fastqsanger.gz
	SRR6653270.fastq.gz	Fastqsanger.gz
	SRR6653280.fastq.gz	Fastqsanger.gz
	SRR6653290.fastq.gz	Fastqsanger.gz
	SRR6653300.fastq.gz	Fastqsanger.gz

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FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis

Project description:FOXO transcription factors are central regulators of longevity from worms to humans. FOXO3 – the FOXO isoform associated with exceptional human longevity – preserves adult neural stem cell pools. Here we identify FOXO3 direct targets genome-wide in primary cultures of adult neural progenitor cells (NPCs). Interestingly, FOXO3-bound sites are enriched for motifs for bHLH transcription factors and FOXO3 shares common targets with the pro-neuronal bHLH transcription factor ASCL1/MASH1 in NPCs. Analysis of the chromatin landscape reveals that FOXO3 and ASCL1 are particularly enriched at the enhancers of genes involved in neurogenic pathways. Intriguingly, FOXO3 inhibits ASCL1-dependent neurogenesis in NPCs and direct neuronal conversion in fibroblasts. FOXO3 also restrains neurogenesis in vivo. Our study identifies a genome-wide interaction between the pro-longevity transcription factor FOXO3 and the cell fate determinant ASCL1, and raises the possibility that FOXO3’s ability to restrain ASCL1-dependent neurogenesis may help preserve the neural stem cell pool. ChIP-seq profiles of two transcription factors (FOXO3 and ASCL1) and three histone marks (H3K4me1, H3K4me3 and H3K27me3) in adult mouse neural progenitor cells.

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