RNF12 Is an X-Encoded Dose-Dependent Activator of X Chromosome Inactivation

被引：194

作者：

Jonkers, Iris ^{[1
,2
]}

Barakat, Tahsin Stefan ^{[1
]}

Achame, Eskeatnaf Mulugeta ^{[1
]}

Monkhorst, Kim ^{[3
]}

Kenter, Annegien ^{[1
]}

Rentmeester, Eveline ^{[1
]}

Grosveld, Frank ^{[2
]}

Grootegoed, J. Anton ^{[1
]}

Gribnau, Joost ^{[1
]}

机构：

[1] Univ Med Ctr, Erasmus MC, Dept Reprod & Dev, NL-3000 CA Rotterdam, Netherlands

[2] Univ Med Ctr, Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands

[3] Univ Med Ctr, Erasmus MC, Dept Expt Pathol, NL-3000 CA Rotterdam, Netherlands

来源：

CELL | 2009年 / 139卷 / 05期

关键词：

XIST GENE; ANTISENSE TRANSCRIPTION; ES CELLS; RNA; CHOICE; PLURIPOTENCY; PROBABILITY; TRANSGENE; NUCLEUS; REPEAT;

D O I：

10.1016/j.cell.2009.10.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

In somatic cells of female placental mammals, one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes. Random X chromosome inactivation (XCI) in the embryo is a stochastic process, in which each X has an independent probability to initiate XCI, triggered by the nuclear concentration of one or more X-encoded XCI-activators. Here, we identify the E3 ubiquitin ligase RNF12 as an important XCI-activator. Additional copies of mouse Rnf12 or human RNF12 result in initiation of XCI in male mouse ES cells and on both X chromosomes in a substantial percentage of female mouse ES cells. This activity is dependent on an intact open reading frame of Rnf12 and correlates with the transgenic expression level of RNF12. Initiation of XCI is markedly reduced in differentiating female heterozygous Rnf12(+/-) ES cells. These findings provide evidence for a dose-dependent role of RNF12 in the XCI counting and initiation process.

引用

页码：999 / 1011

页数：13

共 36 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]

RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex [J].

Bach, I ;

Rodriguez-Esteban, C ;

Carrière, C ;

Bhushan, A ;

Krones, A ;

Rose, DW ;

Glass, CK ;

Andersen, B ;

Belmonte, JCI ;

Rosenfeld, MG .

NATURE GENETICS, 1999, 22 (04) :394-399

[3]

Becker Thomas, 2003, Methods in Cell Science, V25, P85, DOI 10.1023/B:MICS.0000006895.03556.9b

[4]

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

[5]

THE HUMAN XIST GENE - ANALYSIS OF A 17 KB INACTIVE X-SPECIFIC RNA THAT CONTAINS CONSERVED REPEATS AND IS HIGHLY LOCALIZED WITHIN THE NUCLEUS [J].

BROWN, CJ ;

HENDRICH, BD ;

RUPERT, JL ;

LAFRENIERE, RG ;

XING, Y ;

LAWRENCE, J ;

WILLARD, HF .

CELL, 1992, 71 (03) :527-542

[6]

Vive la Difference: Males vs females in flies vs worms [J].

Cline, TW ;

Meyer, BJ .

ANNUAL REVIEW OF GENETICS, 1996, 30 :637-702

[7]

Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch [J].

Donohoe, Mary E. ;

Zhang, Li-Feng ;

Xu, Na ;

Shi, Yang ;

Lee, Jeannie T. .

MOLECULAR CELL, 2007, 25 (01) :43-56

[8]

The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting [J].

Donohoe, Mary E. ;

Silva, Susana S. ;

Pinter, Stefan F. ;

Xu, Na ;

Lee, Jeannie T. .

NATURE, 2009, 460 (7251) :128-U147

[9]

Heard E, 1999, MOL CELL BIOL, V19, P3156

[10]

Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis of TRF1 [J].

Her, Yoon Ra ;

Chung, In Kwon .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (13) :8557-8566

← 1 2 3 4 →