Structural Association of XIST RNA with Inactive Chromosomes in Somatic Cells : a Key Step in the Process that Establishes and Faithfully Maintains X-inactivation
Authors
Clemson, Christine MoultonFaculty Advisor
Jeanne Bentley LawrenceAcademic Program
Cell BiologyUMass Chan Affiliations
NeurologyDocument Type
Doctoral DissertationPublication Date
1998-05-01Keywords
Gene Expression RegulationDosage Compensation (Genetics)
RNA
Genetic Phenomena
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
The XIST gene is implicated in X-chromosome inactivation, yet the RNA contains no apparent open reading frame. An accumulation of XIST RNA is observed near its site of transcription, the inactive X chromosome (Xi). A series of molecular cytogenetic studies comparing properties of XIST RNA to other protein coding RNAs, support a critical distinction for XIST RNA; XIST RNA does not concentrate at Xi simply because it is transcribed and processed there. Most notably, morphometric and 3-D analysis reveals that XIST RNA and Xi are coincident in 2-D and 3-D space; hence the XIST RNA essentially paints Xi. Several results indicate that the XIST RNA accumulation has two components, a minor one associated with transcription and processing, and a spliced major component, which stably associates with Xi. Upon transcriptional inhibition the major spliced component remains in the nucleus and often encircles the extra-prominent heterochromatic Barr body. The continually transcribed XIST gene and its poly-adenylated RNA consistently localize to a nuclear region devoid of splicing factor/poly A RNA rich domains. XIST RNA remains with the nuclear matrix fraction after removal of chromosomal DNA. XIST RNA is released from its association with Xi during mitosis, but shows a unique highly particulate distribution. Collective results indicate that XIST RNA may be an architectural element of the interphase chromosome territory, possibly a component of non-chromatin nuclear structure that specifically associates with Xi. XIST RNA is a novel nuclear RNA which potentially provides a specific precedent for RNA involvement in nuclear structure and cis-limited gene regulation via higher-order chromatin packaging.DOI
10.13028/asf9-7d95Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32167Notes
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Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/asf9-7d95