News Finding: "We showed that the SMCHD1 protein influences gene expression by regulating the folding of the inactive X chromosome into its unique conformation, which prevents expression of its genes," says Chen-Yu Wang, MD, of the MGH Department of Molecular Biology , lead author of the Cell paper.
Paper Finding: We conclude that SMCHD1 plays a critical role in organizing Xi structures by merging chromatin compartments.
News Context: "We showed that the SMCHD1 protein influences gene expression by regulating the folding of the inactive X chromosome into its unique conformation, which prevents expression of its genes," says Chen-Yu Wang, MD, of the MGH Department of Molecular Biology , lead author of the Cell paper. "Mutations in SMCHD1 are associated with several human diseases, including a severe form of muscular dystrophy and a syndrome in which an infant's nose fails to develop. Our finding suggests that misfolded chromatin -- the chromosomal structure consisting of DNA wrapped around proteins called histones -- may play a role in those diseases."
Paper Context: SMCHD1 depletion thus revealed a tendency of Xist-rich and Xist-poor chromatin to form distinct spatial compartments, a hidden layer of architectural organization obscured on the normal Xi. We conclude that SMCHD1 plays a critical role in organizing Xi structures by merging chromatin compartments. Interestingly, however, by employing in situ Hi-C, we observed clearly discernible TADs, albeit weak, across the entire Xi of WT NPCs at 40-kb resolution (Figures 5A and S4C) .