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ChIP-Seq Data Mining: Remarkable Differences in NRSF/REST Target Genes between Human ESC and ESC-Derived Neurons.
Jun-Ichi Satoh1, Natsuki Kawana, Yoji Yamamoto
1Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.
Bioinformatics and Biology Insights
|December 11, 2013
Summary
The neuron-restrictive silencer factor (NRSF) silences neuronal genes in human embryonic stem cells (ESC) more effectively than in derived neurons. This study identifies NRSF targets and reveals differences in binding and pathways between these cell types.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuron-restrictive silencer factor (NRSF) is a transcription factor that represses neuronal gene expression in non-neuronal cells.
- Aberrant NRSF regulation is implicated in neurodegenerative diseases, but its comprehensive target gene set in human neurons is uncharacterized.
- Understanding NRSF function is crucial for neurobiology and disease research.
Purpose of the Study:
- To comprehensively identify neuron-restrictive silencer factor (NRSF) target genes in human embryonic stem cells (ESC) and ESC-derived neurons.
- To analyze differences in NRSF binding sites, target genes, and associated molecular pathways between ESC and ESC-derived neurons.
- To investigate the effectiveness of NRSF-mediated gene silencing in different human cell types.
Main Methods:
- Genome-wide data mining of chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets for NRSF binding sites.
- Utilized bioinformatics tools (Avadis NGS, MACS) for identification and analysis of NRSF target genes.
- Performed motif analysis and pathway enrichment analysis on identified target genes.
Main Results:
- Identified 2,172 NRSF target genes in ESC and 308 in ESC-derived neurons.
- Found only 40 overlapping target genes between ESC and ESC-derived neurons.
- Observed enrichment of consensus RE1 sites in ESC, while ESC-derived neurons showed binding at poorly defined non-RE1 sites.
- NRSF target genes in ESC were linked to neuronal functions (e.g., neuroactive ligand-receptor interaction, CREB signaling, axonal guidance).
- NRSF target genes in ESC-derived neurons were not directed towards neuron-specific functions.
Conclusions:
- NRSF-mediated gene silencing is highly effective in human ESC.
- NRSF-mediated gene silencing is less effective in ESC-derived neurons.
- Significant differences in NRSF target genes and pathways exist between ESC and ESC-derived neurons, highlighting cell-type-specific regulation.
