Chromatin remodeler CHD7 regulates neurogenic gene expression via controlling chromatin accessibility and modifications of histone marks H3K27me3 and H3K4me3 [Human RNA-seq]

CHD7 (Chromo-Helicase-DNA binding protein 7) is an ATP-dependent chromatin remodeler required for neural development. To elucidate the molecular mechanism of the function of CHD7 in neurodevelopment, we performed high-throughput sequencing by RNA-seq, ATAC-seq and CUT&Tag on day 14 human cortical organoids derived from control and CHD7 KO H9 hESCs , as well as RNA-seq and CUT&Tag on E10.5 mouse forebrain which Chd7 was specifically depleted in neuroepithelial cells. We found that CHD7 activates neural stem and progenitor cell-specific transcription factors via regulating chromatin accessibility and modification of histone marks H3K27me3 and H3K4me3 in both human cortical organoids and mouse forebrain. Overall design: To investigate the gene expression change upon loss of CHD7 during the differentiation from ESC to cortical organoids, we established H9 CHD7 KO cell lines by CRISPR-Cas9 technology.