SATB1 Defines the Developmental Context for Gene Silencing by Xist in Lymphoma and Embryonic Cells

被引：159

作者：

Agrelo, Ruben ^{[1
]}

Souabni, Abdallah ^{[1
]}

Novatchkova, Maria ^{[1
]}

Haslinger, Christian ^{[2
]}

Leeb, Martin ^{[1
]}

Komnenovic, Vukoslav ^{[1
]}

Kishimoto, Hiroyuki ^{[1
]}

Gresh, Lionel ^{[1
]}

Kohwi-Shigematsu, Terumi ^{[3
]}

Kenner, Lukas ^{[4
,5
]}

Wutz, Anton ^{[1
]}

机构：

[1] Res Inst Mol Pathol, A-1030 Vienna, Austria

[2] Boehringer Ingelheim Austria, A-1121 Vienna, Austria

[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA

[4] Inst Klin Pathol, A-1090 Vienna, Austria

[5] LBI CR, A-1090 Vienna, Austria

来源：

DEVELOPMENTAL CELL | 2009年 / 16卷 / 04期

基金：

奥地利科学基金会;

关键词：

X-CHROMOSOME INACTIVATION; MAR-BINDING PROTEIN; STEM-CELLS; HISTONE MACROH2A1; EXPRESSION; DIFFERENTIATION; MAINTENANCE; INITIATION; LOCALIZATION; PROPAGATION;

D O I：

10.1016/j.devcel.2009.03.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：507 / 516

页数：10

共 45 条

[1]

Alvarez JD, 2000, GENE DEV, V14, P521

[2] A quantitative matrigel assay for assessing repopulating capacity of prostate stem cells [J].