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  • 1
    Publication Date: 2013-07-06
    Description: Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.〈br /〉〈br /〉〈a href="" target="_blank"〉〈img src="" border="0"〉〈/a〉   〈a href="" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engreitz, Jesse M -- Pandya-Jones, Amy -- McDonel, Patrick -- Shishkin, Alexander -- Sirokman, Klara -- Surka, Christine -- Kadri, Sabah -- Xing, Jeffrey -- Goren, Alon -- Lander, Eric S -- Plath, Kathrin -- Guttman, Mitchell -- 1F32GM103139-01/GM/NIGMS NIH HHS/ -- DP5 OD012190/OD/NIH HHS/ -- DP5OD012190/OD/NIH HHS/ -- P01 GM099134/GM/NIGMS NIH HHS/ -- P01GM099134/GM/NIGMS NIH HHS/ -- P50HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):1237973. doi: 10.1126/science.1237973. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Line ; Chromatin/chemistry/metabolism ; Female ; *Genome ; Male ; Mice ; Models, Genetic ; RNA, Long Noncoding/chemistry/*metabolism ; Transcription, Genetic ; X Chromosome/*metabolism/ultrastructure ; *X Chromosome Inactivation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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