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
Sex based differences in vascular function
TL;DR: Basic research into mechanisms of sex differences in vascular function will result in improved prevention, detection and treatment of cardiovascular disease in both men and women.
Journal ArticleDOI
5-Hydroxymethylcytosine and disease
TL;DR: This work has suggested that 5hmC acts not only as an intermediate in the DNA demethylation process but also as an independent epigenetic marker, playing an important role in the regulation of gene expression.
Journal ArticleDOI
Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases.
Yuanyuan Li,Trygve O. Tollefsbol +1 more
TL;DR: This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease.
Journal ArticleDOI
Antisense regulation in X inactivation and autosomal imprinting.
TL;DR: This article reviews the latest developments in antisense regulation in XCI and autosomal imprinting and speculates on molecular means by which antisense genes can regulate silencing in mammals.
Journal ArticleDOI
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation.
TL;DR: These findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin and suggest that repressive histone modifications such as trimethylated histone 4 lysine 20 in pluripotency and development are largely unknown.
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.
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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.