PT  - JOURNAL ARTICLE
AU  - Fumitaka Inoue
AU  - Anat Kreimer
AU  - Tal Ashuach
AU  - Nadav Ahituv
AU  - Nir Yosef
TI  - Massively parallel characterization of regulatory dynamics during neural induction
AID  - 10.1101/370452
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 370452
4099  - http://biorxiv.org/content/early/2018/07/16/370452.short
4100  - http://biorxiv.org/content/early/2018/07/16/370452.full
AB  - The molecular components governing neural induction remain largely unknown. Here, we applied a suite of genomic and computational tools to comprehensively identify these components. We performed RNA-seq, ChIP-seq (H3K27ac, H3K27me3) and ATAC-seq on human embryonic stem cells (hESCs) at seven early neural differentiation time points (0-72 hours) and identified thousands of induced genes and regulatory regions. We analyzed the function of ~2,500 selected regions using massively parallel reporter assays at all time points. We found numerous temporal enhancers that correlated with similarly timed epigenetic marks and gene expression. Development of a prioritization method that incorporated all genomic data identified key transcription factors (TFs) involved in neural induction. Individual overexpression of eleven TFs and several combinations in hESCs found novel neural induction regulators. Combined, our results provide a comprehensive map of genes and functional regulatory elements involved in neural induction and identify master regulator TFs that are instrumental for this process.One Sentence Summary Using numerous genomic assays and computational tools we characterized the dynamic changes that take place during neural induction.