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Changes in chromatin accessibility and gene expression induced by overexpression of ONECUT transcription factors

ABSTRACT: Changes in chromatin accessibility and gene expression induced by overexpression of ONECUT transcription factors

PROVIDER: PRJNA491706 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7866690_1.fastq.gz	Fastqsanger.gz
	SRR7866690_2.fastq.gz	Fastqsanger.gz
	SRR7866700_1.fastq.gz	Fastqsanger.gz
	SRR7866700_2.fastq.gz	Fastqsanger.gz
	SRR7866930_1.fastq.gz	Fastqsanger.gz

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Profiling of chromatin accessibility in fibroblasts, iPSCs, iPSC-derived neurons and cells overexpressing Onecut transcription factors (OC1, OC2, OC3)

Project description:Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we here used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced neuronal morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights the potential of ONECUT transcription factors for direct neuronal reprogramming.

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Profiling of chromatin accessibility in fibroblasts, iPSCs, iPSC-derived neurons and cells overexpressing Onecut transcription factors (OC1, OC2, OC3)

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Acute BAF perturbation causes immediate changes in chromatin accessibility

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Project description:Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced a neuron-like morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights both the potential and challenges of ONECUT-based direct neuronal reprogramming.

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