GSBS Student Publications

Title

The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences

Student Author(s)

Christine Clemson

GSBS Program

MS in Clinical Investigation

UMMS Affiliation

Department of Cell Biology

Date

5-10-2006

Document Type

Article

Medical Subject Headings

Chromatin; Chromosomes, Human, X; Female; *Gene Silencing; *Genes, X-Linked; Humans; In Situ Hybridization; RNA, Untranslated; Sex Chromatin; Transcription, Genetic; *X Chromosome Inactivation

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

We investigated whether genes escape X chromosome inactivation by positioning outside of the territory defined by XIST RNA. Results reveal an unanticipated higher order organization of genes and noncoding sequences. All 15 X-linked genes, regardless of activity, position on the border of the XIST RNA territory, which resides outside of the DAPI-dense Barr body. Although more strictly delineated on the inactive X chromosome (Xi), all genes localized predominantly to the outer rim of the Xi and active X chromosome. This outer rim is decorated only by X chromosome DNA paints and is excluded from both the XIST RNA and dense DAPI staining. The only DNA found well within the Barr body and XIST RNA territory was centromeric and Cot-1 DNA; hence, the core of the X chromosome essentially excludes genes and is composed primarily of noncoding repeat-rich DNA. Moreover, we show that this core of repetitive sequences is expressed throughout the nucleus yet is silenced throughout Xi, providing direct evidence for chromosome-wide regulation of "junk" DNA transcription. Collective results suggest that the Barr body, long presumed to be the physical manifestation of silenced genes, is in fact composed of a core of silenced noncoding DNA. Instead of acting at a local gene level, XIST RNA appears to interact with and silence core architectural elements to effectively condense and shut down the Xi.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7688-93. Epub 2006 May 8. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

16682630