ENAapplication/xmlftp.sra.ebi.ac.uk/vol1/fastq/SRR501/SRR501035/SRR501035.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR501/SRR501036/SRR501036.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR501/SRR501034/SRR501034.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR501/SRR501033/SRR501033.fastq.gzprimaryOK2000000GenomicsCellular and Molecular Medicine, Bioinformatics, Ottawa Hospital Research Institute, Ontario Genomics Innovation Centre (OGIC)https://www.ebi.ac.uk/ena/browser/view/PRJNA167512Mus musculusIn skeletal myogenesis, the transcription factor MyoD, activates distinct transcriptional programs in progenitors compared to terminally differentiated cells. Using ChIP-seq and gene expression analyses, we show that in primary myoblasts, Snai1/2-HDAC1/2 repressive complex bind and exclude MyoD from its targets. Notably, Snail binds E-box motifs that are G/C-rich in their central dinucleotides, and such sites are almost exclusively associated with genes expressed during differentiation. By contrast, Snai1/2 does not bind the A/T-rich E-boxes associated with MyoD targets in myoblasts. Thus, Snai1/2-HDAC1/2 prevents MyoD occupancy on differentiation-specific regulatory elements and the change from Snail1/2- to MyoD-binding often results in enhancer switching during differentiation. Furthermore, we show that a regulatory network involving Myogenic Regulatory Factors (MRFs), Snail/2, miR-30a and miR-206 acts as a molecular switch that controls entry into myogenic differentiation. Together, these results reveal a regulatory paradigm that directs distinct gene expression programs in progenitors versus terminally differentiated cells. Overall design: In vivo depletion of transcription factor with siRNA followed by whole transcriptome analysis (RNA-seq) to identify target genes.ENAEmbryonic, Precursor Muscle Cell, XSnail2, data, WS2D, Sna, SNA, snai2, Sna1, Embryonic Muscle Cells, SLUG, mice, Precursor, mouse, xSlu, RNA-seq, xsna, AI194338, Muscle Cells, dJ710H13.1, slug, SNAIL, SNAIL1, SNAH, SNAIL2, Embryonic., Mus, Snail, Slug, SLUGH1, SLUGH2, Embryonic Muscle Cell, Whole Transcriptome Shotgun Sequencing, xslug, Mouse, Precursor Muscle Cells, Snail1, house mouse, Snail2, Myoblast, Slugh, Muscle Cellmouse, mouse <Mus musculus>, house mouse.0.00.00.00.00.00falseMus musculusRNA-seq data of si-Snai1, si-Snai2, si-Snai1/2 and si-Scrambled treated mouse primary myoblasts2022-05-122013-05-31PRJNA167512GSE382362277111710090