Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300

被引：808
作者：
Yao, TP
Oh, SP
Fuchs, M
Zhou, ND
Ch'ng, LE
Newsome, D
Bronson, RT
Li, E
Livingston, DM [1 ]
Eckner, R
机构：
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA
[4] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA
[5] Tufts Univ, Sch Vet Med, Boston, MA 02111 USA
[6] Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland
来源：
CELL | 1998年 / 93卷 / 03期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1016/S0092-8674(00)81165-4
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：
The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly, p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.
引用
收藏
页码：361 / 372
页数：12
相关论文
共 55 条
[41]   RUBINSTEIN-TAYBI SYNDROME CAUSED BY MUTATIONS IN THE TRANSCRIPTIONAL COACTIVATOR CBP [J].
PETRIJ, F ;
GILES, RH ;
DAUWERSE, HG ;
SARIS, JJ ;
HENNEKAM, RCM ;
MASUNO, M ;
TOMMERUP, N ;
VANOMMEN, GJB ;
GOODMAN, RH ;
PETERS, DJM ;
BREUNING, MH .
NATURE, 1995, 376 (6538) :348-351
[42]   P300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription [J].
Puri, PL ;
Avantaggiati, ML ;
Balsano, C ;
Sang, NL ;
Graessmann, A ;
Giordano, A ;
Levrero, M .
EMBO JOURNAL, 1997, 16 (02) :369-383
[43]   Molecular mechanisms of myogenic coactivation by p300: Direct interaction with the activation domain of MyoD and with the MADS box of MEF2C [J].
Sartorelli, V ;
Huang, J ;
Hamamori, Y ;
Kedes, L .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (02) :1010-1026
[44]   Transcription factor AP-2 essential for cranial closure and craniofacial development [J].
Schorle, H ;
Meier, P ;
Buchert, M ;
Jaenisch, R ;
Mitchell, PJ .
NATURE, 1996, 381 (6579) :235-238
[45]   CROSS-COUPLING OF SIGNAL TRANSDUCTION PATHWAYS - ZINC FINGER MEETS LEUCINE ZIPPER [J].
SCHULE, R ;
EVANS, RM .
TRENDS IN GENETICS, 1991, 7 (11-12) :377-381
[46]   The p300/CBP family: Integrating signals with transcription factors and chromatin [J].
Shikama, N ;
Lyon, J ;
LaThangue, NB .
TRENDS IN CELL BIOLOGY, 1997, 7 (06) :230-236
[47]   CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription [J].
Smith, CL ;
Onate, SA ;
Tsai, MJ ;
OMalley, BW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (17) :8884-8888
[48]   MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3) [J].
Sobulo, OM ;
Borrow, J ;
Tomek, R ;
Reshmi, S ;
Harden, A ;
Schlegelberger, B ;
Housman, D ;
Doggett, NA ;
Rowley, JD ;
ZeleznikLe, NJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) :8732-8737
[49]   Abnormal skeletal patterning in embryos lacking a single Cbp allele: A partial similarity with Rubinstein-Taybi syndrome [J].
Tanaka, Y ;
Naruse, I ;
Maekawa, T ;
Masuya, H ;
Shiroishi, T ;
Ishii, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (19) :10215-10220
[50]   The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function [J].
Torchia, J ;
Rose, DW ;
Inostroza, J ;
Kamei, Y ;
Westin, S ;
Glass, CK ;
Rosenfeld, MG .
NATURE, 1997, 387 (6634) :677-684
123456