CTCF, a candidate trans-acting factor for X-inactivation choice

被引:219
作者
Chao, W [1 ]
Huynh, KD [1 ]
Spencer, RJ [1 ]
Davidow, LS [1 ]
Lee, JT [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA
关键词
D O I
10.1126/science.1065982
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In mammals, X-inactivation silences one of two female X chromosomes. Silencing depends on the noncoding gene, Xist ((i) under bar nactive (X) under bar-(s) under bar pecific (t) under bar ranscript), and is blocked by the antisense gene, Tsix. Deleting the choice/imprinting center in Tsix affects X-chromosome selection. Here, we identify the insulator and transcription factor, CTCF, as a candidate trans-acting factor for X-chromosome selection. The choice/imprinting center contains tandem CTCF binding sites that function in an enhancer-blocking assay. In vitro binding is reduced by CpG methylation and abolished by including non-CpG methylation. We postulate that Tsix and CTCF together establish a regulatable epigenetic switch for X-inactivation.
引用
收藏
页码:345 / 347
页数:3
相关论文
共 27 条
[1]   X-chromosome inactivation: Counting, choice and initiation [J].
Avner, P ;
Heard, E .
NATURE REVIEWS GENETICS, 2001, 2 (01) :59-67
[2]   The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].
Bell, AC ;
West, AG ;
Felsenfeld, G .
CELL, 1999, 98 (03) :387-396
[3]   Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene [J].
Bell, AC ;
Felsenfeld, G .
NATURE, 2000, 405 (6785) :482-485
[4]   c-Myc target gene specificity is determined by a post-DNA-binding mechanism [J].
Boyd, KE ;
Wells, J ;
Gutman, J ;
Bartley, SM ;
Farnham, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) :13887-13892
[5]   THE PRODUCT OF THE MOUSE XIST GENE IS A 15 KB INACTIVE X-SPECIFIC TRANSCRIPT CONTAINING NO CONSERVED ORF AND LOCATED IN THE NUCLEUS [J].
BROCKDORFF, N ;
ASHWORTH, A ;
KAY, GF ;
MCCABE, VM ;
NORRIS, DP ;
COOPER, PJ ;
SWIFT, S ;
RASTAN, S .
CELL, 1992, 71 (03) :515-526
[6]   LOCALIZATION OF THE X-INACTIVATION CENTER ON THE HUMAN X-CHROMOSOME IN XQ13 [J].
BROWN, CJ ;
LAFRENIERE, RG ;
POWERS, VE ;
SEBASTIO, G ;
BALLABIO, A ;
PETTIGREW, AL ;
LEDBETTER, DH ;
LEVY, E ;
CRAIG, IW ;
WILLARD, HF .
NATURE, 1991, 349 (6304) :82-84
[7]   A GENE FROM THE REGION OF THE HUMAN X-INACTIVATION CENTER IS EXPRESSED EXCLUSIVELY FROM THE INACTIVE X-CHROMOSOME [J].
BROWN, CJ ;
BALLABIO, A ;
RUPERT, JL ;
LAFRENIERE, RG ;
GROMPE, M ;
TONLORENZI, R ;
WILLARD, HF .
NATURE, 1991, 349 (6304) :38-44
[8]   A 5' ELEMENT OF THE CHICKEN BETA-GLOBIN DOMAIN SERVES AS AN INSULATOR IN HUMAN ERYTHROID-CELLS AND PROTECTS AGAINST POSITION EFFECT IN DROSOPHILA [J].
CHUNG, JH ;
WHITELEY, M ;
FELSENFELD, G .
CELL, 1993, 74 (03) :505-514
[9]   XCE HAPLOTYPES SHOW MODIFIED METHYLATION IN A REGION OF THE ACTIVE X-CHROMOSOME LYING 3' TO XIST [J].
COURTIER, B ;
HEARD, E ;
AVNER, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (08) :3531-3535
[10]  
Debrand E, 1999, MOL CELL BIOL, V19, P8513