title: SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells.
abstract: The noncoding Xist RNA triggers silencing of one of the two female X chromosomes during X inactivation in mammals. Gene silencing by Xist is restricted to a special developmental context in early embryos and specific hematopoietic precursors. Here, we show that Xist can initiate silencing in a lymphoma model. We identify the special AT-rich binding protein SATB1 as an essential silencing factor. Loss of SATB1 in tumor cells abrogates the silencing function of Xist. In lymphocytes Xist localizes along SATB1-organized chromatin and SATB1 and Xist influence each other's pattern of localization. SATB1 and its homolog SATB2 are expressed during the initiation window for X inactivation in ES cells. Importantly, viral expression of SATB1 or SATB2 enables gene silencing by Xist in embryonic fibroblasts, which normally do not provide an initiation context. Thus, our data establish SATB1 as a crucial silencing factor contributing to the initiation of X inactivation.
authors.affiliation: Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Ruben
authors.initials: R
authors.lastname: Agrelo
authors.forename: Abdallah
authors.initials: A
authors.lastname: Souabni
authors.forename: Maria
authors.initials: M
authors.lastname: Novatchkova
authors.forename: Christian
authors.initials: C
authors.lastname: Haslinger
authors.forename: Martin
authors.initials: M
authors.lastname: Leeb
authors.forename: Vukoslav
authors.initials: V
authors.lastname: Komnenovic
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Lionel
authors.initials: L
authors.lastname: Gresh
authors.forename: Terumi
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Anton
authors.initials: A
authors.lastname: Wutz
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008223:Lymphoma / Q000196:embryology* / Q000473:pathology; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D034443:RNA Transport; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C469541:Satb1 protein, mouse; C077885:XIST non-coding RNA