Site-specific silencing of regulatory elements as a mechanism of X inactivation.
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.
Duke Scholars
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Related Subject Headings
- X Chromosome Inactivation
- Trophoblasts
- Stem Cells
- Repressor Proteins
- Regulatory Elements, Transcriptional
- RNA Polymerase II
- Polycomb-Group Proteins
- Mice
- Long Interspersed Nucleotide Elements
- Histone Code
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- X Chromosome Inactivation
- Trophoblasts
- Stem Cells
- Repressor Proteins
- Regulatory Elements, Transcriptional
- RNA Polymerase II
- Polycomb-Group Proteins
- Mice
- Long Interspersed Nucleotide Elements
- Histone Code