Neil Brockdorff

Abstract The chromosomal protein SMCHD1 is a GHKL ATPase with important roles in epigenetic silencing, including on the inactive X chromosome (Xi). Mutations of SMCHD1 have been linked to facioscapulohumeral muscular dystrophy (FSHD) and Bosma arrhinia microphthalmia syndrome (BAMS). Here, we use live-cell and single-molecule imaging to investigate SMCHD1 interactions with chromatin and its function in epigenetic silencing.

Abstract The non-coding RNA Xist mediates X chromosome inactivation (XCI) in mammals, functioning in cis to direct heterochromatin formation over a single X chromosome in cells of early female embryos. Prior studies have determined that Xist transcription and turnover are modulated to maintain the correct level of Xist RNA to inactivate a single X chromosome. The underlying molecular mechanisms are poorly understood.

Abstract In mammals, chromosome-wide regulatory mechanisms ensure a balance of X-linked gene dosage between males (XY) and females (XX). In female cells, expression of genes from one of the two X chromosomes is curtailed, with selective accumulation of Xist-RNA, Xist-associated proteins, specific histone modifications (for example, H3K27me3) and Barr body formation observed throughout interphase.