PLX071855

GSE112041: RNA-seq in Smchd1 wild-type and Smchd1 null presomitic mesoderm from E9.5 embryos

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loci. Smchd1 deletion in differentiating ES cells results in failed Hox gene silencing and Smchd1 null E9.5 embryos show altered Hox gene expression.. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping. SOURCE: Marnie Blewitt (blewitt@wehi.edu.au) - Blewitt Lab Walter and Eliza Hall Institute