Journal ArticleDOI
X-chromosome inactivation: counting, choice and initiation
Philip Avner,Edith Heard +1 more
TLDR
In many sexually dimorphic species, a mechanism is required to ensure equivalent levels of gene expression from the sex chromosomes, and in mammals, such dosage compensation is achieved by X-chromosome inactivation, a process that presents a unique medley of biological puzzles.Abstract:
In many sexually dimorphic species, a mechanism is required to ensure equivalent levels of gene expression from the sex chromosomes. In mammals, such dosage compensation is achieved by X-chromosome inactivation, a process that presents a unique medley of biological puzzles: how to silence one but not the other X chromosome in the same nucleus; how to count the number of X's and keep only one active; how to choose which X chromosome is inactivated; and how to establish this silent state rapidly and efficiently during early development. The key to most of these puzzles lies in a unique locus, the X-inactivation centre and a remarkable RNA — Xist — that it encodes.read more
Citations
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Journal ArticleDOI
DNA hypomethylation and human diseases.
TL;DR: How global demethylation of repeat sequences including transposable elements and the site-specific hypomethylation of certain genes might contribute to the deleterious effects that ultimately result in the initiation and progression of cancer and other diseases is considered.
Journal ArticleDOI
Chromosomal silencing and localization are mediated by different domains of Xist RNA
TL;DR: It is shown that chromosomal association and spreading of Xist RNA can be functionally separated from silencing by specific mutations.
Journal ArticleDOI
Fast and reliable prediction of noncoding RNAs
TL;DR: All of the known noncoding RNAs and cis-acting elements with high significance are recovered and compelling evidence for many other conserved RNA secondary structures not described so far to the authors' knowledge is found.
The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome
Jesse M. Engreitz,Amy Pandya-Jones,Patrick McDonel,Alexander A. Shishkin,Klara Sirokman,Christine Surka,Sabah Kadri,Jeffrey C. Xing,Alon Goren,Eric S. Lander,Eric S. Lander,Eric S. Lander,Kathrin Plath,Mitchell Guttman +13 more
TL;DR: The data suggest a model for how Xist can integrate its two functions—localization to DNA and silencing of gene expression—to coat the entire X chromosome.
BookDOI
Long Noncoding RNAs
TL;DR: The chapter shows that the current understanding of what is a gene should be revised, in order to clearly define the complex relationship between product-coding regions, regulatory sequences, and the organism’s phenotype.
References
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Journal ArticleDOI
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
Journal ArticleDOI
Demethylation of the zygotic paternal genome
TL;DR: It is shown that the paternal genome in the mouse is significantly and actively demethylated within 6–8 hours of fertilization, before the onset of DNA replication, whereas the maternal genome is dem methylated after several cleavage divisions.
Journal ArticleDOI
Requirement for Xist in X chromosome inactivation
Graeme D. Penny,Graham F. Kay,Graham F. Kay,Steven A. Sheardown,Sohaila Rastan,Sohaila Rastan,Neil Brockdorff +6 more
TL;DR: Evidence for gene targeting of Xist, the proposed candidate for the X inactivation centre, is provided, and its absolute requirement in the process of X chromosome inactivation is provided.
Journal ArticleDOI
Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene.
Guoliang Xu,Timothy H. Bestor,Déborah Bourc'his,Chih-Lin Hsieh,Niels Tommerup,Merete Bugge,Maj Hultén,Xiaoyan Qu,James J. Russo,E. Viegas-Péquignot +9 more
TL;DR: It is shown that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6), which is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns.
Journal ArticleDOI
Tsix , a gene antisense to Xist at the X-inactivation centre
TL;DR: Tsix RNA is a 40-kb RNA originating 15 kb downstream of Xist and transcribed across the Xist locus and has features suggesting a role in regulating the early steps of X inactivation, but not the silencing step.