Mechanistic insights into chromosome-wide silencing in X inactivation

• Published in: Human genetics Vol. 130; no. 2; pp. 295 - 305
• Main Authors: Arthold, Susanne, Kurowski, Agata, Wutz, Anton
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-08-2011; Springer; Springer Nature B.V
• Subjects: Animals; Base Pairing; Biomedical and Life Sciences; Biomedicine; Cell cycle; Cell division; Epigenesis, Genetic - physiology; Female; Females; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Gene Function; Genes; Heterochromatin - physiology; Human Genetics; Humans; Kinases; Localization; Mammals; Metabolic Diseases; Molecular Medicine; Review Paper; RNA; RNA polymerase; RNA, Long Noncoding; RNA, Untranslated - genetics; RNA, Untranslated - physiology; Transcription factors; X Chromosome - physiology; X Chromosome Inactivation - physiology; X chromosomes; Gene Silence; Chromatin Modification; Gene Repression; Mouse Embryonic Stem Cell; Chromosome Territory
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-011-1002-0

In mammals, one of the two X chromosomes in female cells is transcriptionally silenced for dosage compensation between the sexes. Chromosome-wide silencing is initiated by the non-coding
Xist
RNA that accumulates within the inactive X chromosome territory and triggers gene repression and chromatin modifications. Epigenetic changes of the inactive X chromosome in a developmentally regulated manner result in stable gene repression in female somatic cells. X inactivation is a model for understanding the formation of facultative heterochromatin in mammalian development and represents a paradigm for RNA mediated regulation of gene expression. In this review, we summarize the present knowledge of the mechanism of chromosome-wide silencing and give an outlook on future directions.