Abstract |
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.
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Authors | J Mauro Calabrese, Wei Sun, Lingyun Song, Joshua W Mugford, Lucy Williams, Della Yee, Joshua Starmer, Piotr Mieczkowski, Gregory E Crawford, Terry Magnuson |
Journal | Cell
(Cell)
Vol. 151
Issue 5
Pg. 951-63
(Nov 21 2012)
ISSN: 1097-4172 [Electronic] United States |
PMID | 23178118
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- CCCTC-Binding Factor
- Chromatin
- Ctcf protein, mouse
- Polycomb-Group Proteins
- Repressor Proteins
- RNA Polymerase II
- Deoxyribonuclease I
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Topics |
- Animals
- CCCTC-Binding Factor
- Chromatin
(metabolism)
- Deoxyribonuclease I
(metabolism)
- Gene Silencing
- Histone Code
- Long Interspersed Nucleotide Elements
- Mice
- Polycomb-Group Proteins
(metabolism)
- RNA Polymerase II
(metabolism)
- Regulatory Elements, Transcriptional
- Repressor Proteins
(metabolism)
- Stem Cells
(cytology, metabolism)
- Trophoblasts
(cytology)
- X Chromosome Inactivation
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