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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Catalytic Properties and Kinetic Mechanism of Human Recombinant Lys-9 Histone H3 Methyltransferase SUV39H1: Participation of the Chromodomain in Enzymatic Catalysis†
TL;DR: A reduction in the level of methylation was observed at high concentrations of rH3, implying substrate inhibition, and a random mechanism in a bi-bi reaction for recombinant SUV39H1 in which either substrate can bind to the enzyme first and either product can release first is suggested.
Journal ArticleDOI
The epigenetic control of antigenic variation in Plasmodium falciparum.
Stuart A. Ralph,Artur Scherf +1 more
TL;DR: Findings indicate that reversible chromatin modifications and perinuclear gene movement are epigenetic factors that define the silent and active states of telomere-adjacent var genes.
Journal ArticleDOI
The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents.
Melina Mitsiogianni,Georgios Koutsidis,Nikos Mavroudis,Dimitrios T. Trafalis,Sotiris Botaitis,Rodrigo Franco,Vasilis Zoumpourlis,Tom Amery,Alex Galanis,Aglaia Pappa,Mihalis I. Panayiotidis +10 more
TL;DR: A number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells, and could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.
Journal ArticleDOI
Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome
TL;DR: This work has identified two macrochromatin domains within macroH2A that are independently capable of MCB formation and association with the Xi, indicating that the histone portion alone can target the Xi.
Journal ArticleDOI
Skewing X chromosome choice by modulating sense transcription across the Xist locus
Tatyana B. Nesterova,Colette M. Johnston,Ruth Appanah,Alistair E. T. Newall,Jonathan Godwin,Maria Alexiou,Neil Brockdorff +6 more
TL;DR: Analysis of a series of targeted mutations at the 5' end of the Xist locus indicates that X chromosome choice is determined by the balance of Xist sense and antisense transcription prior to the onset of random X inactivation.
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.