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
More filters
Book ChapterDOI
The Fetal Matrix: Evolution, Development and Disease: Mother and fetus
Peter D. Gluckman,Mark A. Hanson +1 more
TL;DR: In the previous chapter as mentioned in this paper, we introduced the concept that different phenotypes can arise from the same genotype and introduced two additional concepts about such interactions, the first is that gene-environment interactions are more likely to have a major impact on phenotype if they occur early in life, and the second is that an irreversible change in phenotype acting early-in life can have consequences if the environment later changes.
Journal ArticleDOI
RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes.
Elin Enervald,Elin Enervald,Lynn M. Powell,Lora Boteva,Rossana Foti,Nerea Blanes Ruiz,Gözde Kibar,Agnieszka Piszczek,Fatima Cavaleri,Martin Vingron,Andrea Cerase,Sara B.C. Buonomo,Sara B.C. Buonomo +12 more
TL;DR: This article showed that the mutual exclusion of Tsix and RIF1 at the Xist promoters established a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X-chromosome state.
Journal ArticleDOI
Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novel Xce allele associated with copy number changes.
Kathie Y. Sun,Daniel Oreper,Sarah A. Schoenrock,Rachel C. McMullan,Paola Giusti-Rodríguez,Vasyl Zhabotynsky,Darla R. Miller,Lisa M. Tarantino,Fernando Pardo-Manuel de Villena,William Valdar +9 more
TL;DR: Inter-individual variability in XCI suggests mouse epiblasts contain on average 20-30 cells contributing to brain and NOD/ShiLtJ has a novel and unique functional allele, Xcef, that is the weakest in the Xce allelic series.
Journal ArticleDOI
X-chromosome genetic association test incorporating X-chromosome inactivation and imprinting effects
TL;DR: The proposed MLRXCII test is valid and powerful in genetic association studies on X-chromosome for qualitative traits and thus is recommended in practice.
References
More filters
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.