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. 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.