The Trans-Activator RNF12 and Cis-Acting Elements Effectuate X Chromosome Inactivation Independent of X-Pairing

被引:55
作者
Barakat, Tahsin Stefan [1 ]
Loos, Friedemann [1 ]
van Staveren, Selma [1 ]
Myronova, Elvira [1 ]
Ghazvini, Mehrnaz [1 ,2 ]
Grootegoed, J. Anton [1 ]
Gribnau, Joost [1 ]
机构
[1] Erasmus MC, Univ Med Ctr, Dept Reprod & Dev, Rotterdam, Netherlands
[2] Erasmus MC, Univ Med Ctr, Erasmus Stem Cell Inst, Rotterdam, Netherlands
关键词
CHROMATIN-STRUCTURE; NONCODING RNA; PLURIPOTENCY; CTCF; EXPRESSION; ACTIVATOR; REGION; TSIX; JPX;
D O I
10.1016/j.molcel.2014.02.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
X chromosome inactivation (XCI) in female placental mammals is a vital mechanism for dosage compensation between X-linked and autosomal genes. XCI starts with activation of Xist and silencing of the negative regulator Tsix, followed by cis spreading of Xist RNA over the future inactive X chromosome (Xi). Here, we show that XCI does not require physical contact between the two X chromosomes (X-pairing) but is regulated by trans-acting diffusible factors. We found that the X-encoded trans-acting and dose-dependent XCI-activator RNF12 acts in concert with the cis-regulatory region containing Jpx, Ftx, and Xpr to activate Xist and to overcome repression by Tsix. RNF12 acts at two subsequent steps; two active copies of Rnf12 drive initiation of XCI, and one copy needs to remain active to maintain XCI toward establishment of the Xi. This two-step mechanism ensures that XCI is very robust and fine-tuned, preventing XCI of both X chromosomes.
引用
收藏
页码:965 / 978
页数:14
相关论文
共 30 条
[1]   Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic [J].
Augui, S. ;
Filion, G. J. ;
Huart, S. ;
Nora, E. ;
Guggiari, M. ;
Maresca, M. ;
Stewart, A. F. ;
Heard, E. .
SCIENCE, 2007, 318 (5856) :1632-1636
[2]   Regulation of X-chromosome inactivation by the X-inactivation centre [J].
Augui, Sandrine ;
Nora, Elphege P. ;
Heard, Edith .
NATURE REVIEWS GENETICS, 2011, 12 (06) :429-442
[3]  
Bacher CP, 2006, NAT CELL BIOL, V8, P293, DOI 10.1038/ncb1365
[4]   Precise BAC targeting of genetically polymorphic mouse ES cells [J].
Barakat, Tahsin Stefan ;
Rentmeester, Eveline ;
Sleutels, Frank ;
Grootegoed, J. Anton ;
Gribnau, Joost .
NUCLEIC ACIDS RESEARCH, 2011, 39 (18) :e121
[5]   RNF12 Activates Xist and Is Essential for X Chromosome Inactivation [J].
Barakat, Tahsin Stefan ;
Gunhanlar, Nilhan ;
Pardo, Cristina Gontan ;
Achame, Eskeatnaf Mulugeta ;
Ghazvini, Mehrnaz ;
Boers, Ruben ;
Kenter, Annegien ;
Rentmeester, Eveline ;
Grootegoed, J. Anton ;
Gribnau, Joost .
PLOS GENETICS, 2011, 7 (01)
[6]   X-changing information on X inactivation [J].
Barakat, Tahsin Stefan ;
Jonkers, Iris ;
Monkhorst, Kim ;
Gribnau, Joost .
EXPERIMENTAL CELL RESEARCH, 2010, 316 (05) :679-687
[7]   CHARACTERIZATION OF A MURINE GENE EXPRESSED FROM THE INACTIVE X-CHROMOSOME [J].
BORSANI, G ;
TONLORENZI, R ;
SIMMLER, MC ;
DANDOLO, L ;
ARNAUD, D ;
CAPRA, V ;
GROMPE, M ;
PIZZUTI, A ;
MUZNY, D ;
LAWRENCE, C ;
WILLARD, HF ;
AVNER, P ;
BALLABIO, A .
NATURE, 1991, 351 (6324) :325-329
[8]   CONSERVATION OF POSITION AND EXCLUSIVE EXPRESSION OF MOUSE XIST FROM THE INACTIVE X-CHROMOSOME [J].
BROCKDORFF, N ;
ASHWORTH, A ;
KAY, GF ;
COOPER, P ;
SMITH, S ;
MCCABE, VM ;
NORRIS, DP ;
PENNY, GD ;
PATEL, D ;
RASTAN, S .
NATURE, 1991, 351 (6324) :329-331
[9]   Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region [J].
Chureau, Corinne ;
Chantalat, Sophie ;
Romito, Antonio ;
Galvani, Angelique ;
Duret, Laurent ;
Avner, Philip ;
Rougeulle, Claire .
HUMAN MOLECULAR GENETICS, 2011, 20 (04) :705-718
[10]   Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation [J].
Csankovszki, G ;
Panning, B ;
Bates, B ;
Pehrson, JR ;
Jaenisch, R .
NATURE GENETICS, 1999, 22 (04) :323-324