Site-specific silencing of regulatory elements as a mechanism of X inactivation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Calabrese, JM; Sun, W; Song, L; Mugford, JW; Williams, L; Yee, D; Starmer, J; Mieczkowski, P; Crawford, GE; Magnuson, T

Published Date

  • November 21, 2012

Published In

Volume / Issue

  • 151 / 5

Start / End Page

  • 951 - 963

PubMed ID

  • 23178118

Pubmed Central ID

  • 23178118

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2012.10.037

Language

  • eng

Conference Location

  • United States