Department of Neurology; Lawrence Lab
Cell Biology | Developmental Biology | Genetics and Genomics | Molecular Biology
XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoring XIST, but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact with XIST RNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA 'coats' euchromatin and may impact chromosome architecture in a manner opposite of XIST A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'.
SAF-A, X-inactivation, XIST, nuclear matrix, nuclear scaffold
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© 2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
DOI of Published Version
Philos Trans R Soc Lond B Biol Sci. 2017 Nov 5;372(1733). pii: 20160360. doi: 10.1098/rstb.2016.0360. Link to article on publisher's site
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Creamer K, Lawrence JB. (2017). XIST RNA: a window into the broader role of RNA in nuclear chromosome architecture. Open Access Articles. https://doi.org/10.1098/rstb.2016.0360. Retrieved from https://escholarship.umassmed.edu/oapubs/3314
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This work is licensed under a Creative Commons Attribution 4.0 License.