X chromosome inactivation (XCI) is the phenomenon through which one of the two X chromosomes in female mammals is silenced to achieve dosage compensation with males. XCI is a highly complex, tightly controlled and developmentally regulated process. The mouse undergoes two forms of XCI: imprinted, which occurs in all cells of the preimplantation embryo and in the extraembryonic lineage, and random, which occurs in somatic cells after implantation. This review presents results and hypotheses that have recently been proposed concerning important aspects of both imprinted and random XCI in mice. We focus on how imprinted XCI occurs during preimplantation development, including a brief discussion of the debate as to when silencing initiates. We also discuss regulation of random XCI, focusing on the requirement for Tsix antisense transcription through the Xist locus, on the regulation of Xist chromatin structure by Tsix and on the effect of Tsix regulatory elements on choice and counting. Finally, we review exciting new data revealing that X chromosomes co-localize during random XCI. To conclude, we highlight other aspects of X-linked gene regulation that make it a suitable model for epigenetics at work.
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http://dx.doi.org/10.1016/j.ydbio.2006.07.011 | DOI Listing |
In mammals, X-linked dosage compensation involves two processes: X-chromosome inactivation (XCI) to balance X chromosome dosage between males and females, and hyperactivation of the remaining X chromosome (Xa-hyperactivation) to achieve X-autosome balance in both sexes. Studies of both processes have largely focused on coding genes and have not accounted for transposable elements (TEs) which comprise 50% of the X-chromosome, despite TEs being suspected to have numerous epigenetic functions. This oversight is due in part to the technical challenge of capturing repeat RNAs, bioinformatically aligning them, and determining allelic origin.
View Article and Find Full Text PDFEndocr J
December 2024
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Over 70 intragenic copy-number variations (CNVs) of PHEX have been identified in patients with X-linked hypophosphatemia (XLH). However, the underlying mechanism of these CNVs has been poorly investigated. Furthermore, although PHEX undergoes X chromosome inactivation (XCI), the association between XLH in women with heterozygous PHEX variants and skewed XCI remains unknown.
View Article and Find Full Text PDFJ Pediatr Endocrinol Metab
December 2024
Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Objectives: Mutations in the gene are the most common cause of nephrogenic diabetes insipidus(NDI). In-frame deletions of the gene are a rare variant that results in NDI. We report a novel variant of the p.
View Article and Find Full Text PDFMol Psychiatry
December 2024
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France.
J Med Genet
November 2024
Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan
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