title: A Tale of Two Cities: How Xist and its partners localize to and silence the bicompartmental X.
abstract: Sex chromosomal dosage compensation in mammals takes the form of X chromosome inactivation (XCI), driven by the non-coding RNA Xist. In contrast to dosage compensation systems of flies and worms, mammalian XCI has to restrict its function to the Xist-producing X chromosome, while leaving autosomes and active X untouched. The mechanisms behind the long-range yet cis-specific localization and silencing activities of Xist have long been enigmatic, but genomics, proteomics, super-resolution microscopy, and innovative genetic approaches have produced significant new insights in recent years. In this review, I summarize and integrate these findings with a particular focus on the redundant yet mutually reinforcing pathways that enable long-term transcriptional repression throughout the soma. This includes an exploration of concurrent epigenetic changes acting in parallel within two distinct compartments of the inactive X. I also examine how Polycomb repressive complexes 1 and 2 and macroH2A may bridge XCI establishment and maintenance. XCI is a remarkable phenomenon that operates across multiple scales, combining changes in nuclear architecture, chromosome topology, chromatin compaction, and nucleosome/nucleotide-level epigenetic cues. Learning how these pathways act in concert likely holds the answer to the riddle posed by Cattanach's and other autosomal translocations: What makes the X especially receptive to XCI?
authors.affiliation: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-6403, USA. Electronic address: spinter@uchc.edu.
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Pinter
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D008954:Models, Biological; D062085:RNA, Long Noncoding / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D002843:Chromatin; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA
keywords: Chromatin compaction; Chromosome topology; Gene silencing; Nuclear matrix; Pluripotency; Replication timing