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
Journal ArticleDOI
Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines.
Els Henckaerts,Hartmut Geiger,Jessica C. Langer,Patricia Rebollo,Gary Van Zant,Hans-Willem Snoeck +5 more
TL;DR: Genetic variation in the response to cytokines critical for hematopoiesis in vivo and in the pool size of cells belonging to a phenotype used to isolate essentially pure primitive progenitor and stem cells are demonstrated and loci that may be relevant to the regulation of he matopoietic stem cells in steady state are identified.
Journal ArticleDOI
Variability of X chromosome inactivation: effect on levels of TIMP1 RNA and role of DNA methylation.
TL;DR: Investigation of the contribution of methylation at the promoter to expression level variation and found that methylation of the TIMP1 promoter correlated with instability and low level expression, whereas stable TIMP 1 expression from the inactive X equivalent to that seen from the active X chromosome was observed when the promoter was unmethylated.
Book ChapterDOI
Mechanisms and Dynamics of Heterochromatin Formation During Mammalian Development: Closed Paths and Open Questions
TL;DR: The role of RNA as a regulator of heterochromatic loci also in early embryogenesis has been discussed in this paper, where the authors postulate that the plasticity of the cells in the early embryo relies on the distinctive heter-chromatin features that prevail during embryogenesis and discuss recent findings on the mechanisms driving heter-romatin formation after fertilization.
Journal ArticleDOI
Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells
Tatyana B. Nesterova,Claire E. Senner,Claire E. Senner,Janina Schneider,Janina Schneider,Tilly Alcayna-Stevens,Anna Tattermusch,Myriam Hemberger,Neil Brockdorff +8 more
TL;DR: It is concluded that Tsix and pluripotency factors act synergistically to repress Xist in undifferentiated embryonic stem cells.
Book ChapterDOI
X-chromosome inactivation in mouse embryonic stem cells: analysis of histone modifications and transcriptional activity using immunofluorescence and FISH.
TL;DR: This chapter outlines various techniques for analyzing X-inactivation kinetics in differentiating Embryonic stem (ES) cells, particularly on changing patterns of histone modifications during X inactivation, using immunuofluorescence combined with RNA fluorescence in situ hybridization (FISH) on interphase nuclei, as well as metaphase chromosome staining combined with DNA FISH.
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.