Structural Association of XIST RNA with Inactive Chromosomes in Somatic Cells : a Key Step in the Process that Establishes and Faithfully Maintains X-inactivation
AuthorsClemson, Christine Moulton
Faculty AdvisorJeanne Bentley Lawrence
Academic ProgramCell Biology
UMass Chan AffiliationsNeurology
Document TypeDoctoral Dissertation
KeywordsGene Expression Regulation
Dosage Compensation (Genetics)
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractThe 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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32167
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