SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells.
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.
Agrelo
Ruben
R
Research Institute of Molecular Pathology, Vienna, Austria.
Souabni
Abdallah
A
Novatchkova
Maria
M
Haslinger
Christian
C
Leeb
Martin
M
Komnenovic
Vukoslav
V
Kishimoto
Hiroyuki
H
Gresh
Lionel
L
Kohwi-Shigematsu
Terumi
T
Kenner
Lukas
L
Wutz
Anton
A
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
D036961:Matrix Attachment Region Binding Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C469541:Satb1 protein, mouse; C077885:XIST non-coding RNA