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A conserved noncoding locus regulates random monoallelic Xist expression across a topological boundary

Item Type:Article
Title:A conserved noncoding locus regulates random monoallelic Xist expression across a topological boundary
Creators Name:Galupa, R. and Nora, E.P. and Worsley-Hunt, R. and Picard, C. and Gard, C. and van Bemmel, J.G. and Servant, N. and Zhan, Y. and El Marjou, F. and Johanneau, C. and Diabangouaya, P. and Le Saux, A. and Lameiras, S. and Pipoli da Fonseca, J. and Loos, F. and Gribnau, J. and Baulande, S. and Ohler, U. and Giorgetti, L. and Heard, E.
Abstract:cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.
Keywords:TADs, X-Inactivation, cis-Regulatory Landscape, Gene Regulation, Noncoding RNA, Silencer, Enhancer, Xist, Linx, 5C, Animals, Mice
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Date:20 November 2019
Official Publication:https://doi.org/10.1016/j.molcel.2019.10.030
PubMed:View item in PubMed

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