Skip to main content

Paper titled “Site-Specific Silencing of Regulatory Elements as a Mechanism of X Inactivation.”

Mauro Calabrese, a postdoctoral fellow in Terry Magnuson’s lab, is first-author of an article in Cell entitled Site-Specific Silencing of Regulatory Elements as a Mechanism of X Inactivation.” Coauthors with current or previous Department of Genetics affiliations are Wei Sun, Joshua Mugford, Lucy Williams, Della Yee, Joshua Starmer, and Piotr Mieczkowski, with Terry as senior author.


“The inactive X chromosome’s (Xi) physical territory is microscopically devoid of transcriptional hallmarks and enriched in silencing-associated modifications. How these microscopic signatures relate to specific Xi sequences is unknown. Therefore, we profiled Xi gene expression and chromatin states at high resolution via allele-specific sequencing in mouse trophoblast stem cells. Most notably, X-inactivated transcription start sites harbored distinct epigenetic signatures relative to surrounding Xi DNA. These sites displayed H3-lysine27-trimethylation enrichment and DNaseI hypersensitivity, similar to autosomal Polycomb targets, yet excluded Pol II and other transcriptional hallmarks, similar to nontranscribed genes. CTCF bound X-inactivated and escaping genes, irrespective of measured chromatin boundaries. Escape from X inactivation occurred within, and X inactivation was maintained exterior to, the area encompassed by Xist in cells subject to imprinted and random X inactivation. The data support a model whereby inactivation of specific regulatory elements, rather than a simple chromosome-wide separation from transcription machinery, governs gene silencing over the Xi.”


“► RNA-Seq analysis finds 13% of genes escape X inactivation in trophoblast stem cells ► Inactive X regulatory elements lack Pol II binding yet retain DNaseI hypersensitivity ► CTCF binds across the inactive X, mostly to locations shared with the active X ► X-inactivated genes near escapers are often separated from the measured Xist cloud.”

View the article online in Cell 151(6): 951-963, 2012.