LINE-1 Activity in Facultative Heterochromatin Formation during X Chromosome Inactivation

• Published in: Cell Vol. 141; no. 6; pp. 956 - 969
• Main Authors: Chow, Jennifer C., Ciaudo, Constance, Fazzari, Melissa J., Mise, Nathan, Servant, Nicolas, Glass, Jacob L., Attreed, Matthew, Avner, Philip, Wutz, Anton, Barillot, Emmanuel, Greally, John M., Voinnet, Olivier, Heard, Edith
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.06.2010; Elsevier
• Subjects: Animals; Cell Line; Cellular Biology; DEVBIO; DNA; Embryonic Stem Cells; Embryonic Stem Cells - metabolism; Female; Heterochromatin; Heterochromatin - metabolism; Humans; Life Sciences; Long Interspersed Nucleotide Elements; Mice; RNA; RNA, Long Noncoding; RNA, Untranslated; RNA, Untranslated - metabolism; Transcription, Genetic; X Chromosome; X Chromosome - metabolism; X Chromosome Inactivation; RNA; DNA; DEVBIO
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2010.04.042

During X chromosome inactivation (XCI), Xist RNA coats and silences one of the two X chromosomes in female cells. Little is known about how XCI spreads across the chromosome, although LINE-1 elements have been proposed to play a role. Here we show that LINEs participate in creating a silent nuclear compartment into which genes become recruited. A subset of young LINE-1 elements, however, is expressed during XCI, rather than being silenced. We demonstrate that such LINE expression requires the specific heterochromatic state induced by Xist. These LINEs often lie within escape-prone regions of the X chromosome, but close to genes that are subject to XCI, and are associated with putative endo-siRNAs. LINEs may thus facilitate XCI at different levels, with silent LINEs participating in assembly of a heterochromatic nuclear compartment induced by Xist, and active LINEs participating in local propagation of XCI into regions that would otherwise be prone to escape. [Display omitted] [Display omitted] ► LINE and SINE repeats help to nucleate heterochromatin during X inactivation ► Young LINEs are active on the X chromosome during its inactivation ► Young LINE expression on the inactive X requires functional Xist RNA ► LINE activity may facilitate X inactivation of genes in escape-prone regions