XIST RNA: a window into the broader role of RNA in nuclear chromosome architecture. (5th November 2017)

• Record Type: Journal Article
• Authors: Creamer, K. M.; Lawrence, J. B.
• Is Part Of: Philosophical transactions. Volume 372:Number 1733(2017)
• Publication Date: 2017-11-05
• Subjects: XIST -- X-inactivation -- SAF-A -- nuclear matrix -- nuclear scaffold; Biology -- Periodicals; Science -- Periodicals; 570
• DOI: 10.1098/rstb.2016.0360
• Languages: English
• ISSNs: 0962-8436

Abstract

Abstract : 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'.