Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro

被引:171
作者
Näär, AM
Beaurang, PA
Robinson, KM
Oliner, JD
Avizonis, D
Scheek, S
Zwicker, J
Kadonaga, JT
Tjian, R [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[2] Univ Calif San Diego, Dept Biol, La Jolla, CA 92092 USA
[3] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75235 USA
关键词
transcription; sp1; chromatin; TAFs; coactivators; SREBP1a; CBP; LDLR;
D O I
10.1101/gad.12.19.3020
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The promoter selectivity factor Sp1 often cooperates with other enhancer-binding proteins to activate transcription. To study the molecular underpinnings of these regulatory events, we have reconstituted in vitro the synergy observed in vivo between Sp1 and the sterol-regulated factor SREBP-1a at the low density lipoprotein receptor (LDLR) promoter. Using a highly purified human transcription system, we found that chromatin, TAFs, and a novel SREBP-binding coactivator activity, which includes CBP, are all required to mediate full synergistic activation by Sp1 and SREBP-1a. The SREBP-binding domain of CBP inhibits activation by SREBP-1a and Sp1 in a dominant-negative fashion that is both chromatin- and activator-specific. Whereas recombinant CBP alone is not sufficient to mediate activation, a human cellular fraction containing CBP can support high levels of chromatin-dependent synergistic activation. Purification of this activity to near homogeneity resulted in the identification of a multiprotein coactivator, including CBP, that selectively binds to the SREBP-1a activation domain and is capable of mediating high levels of synergistic activation by SREBP/Sp1 on chromatin templates. The development of a reconstituted chromatin transcription system has allowed us to isolate a novel coactivator that is recruited by the SREBP-1a activation domain and that functions in concert with TFIID to coordinate the action of multiple activators at complex promoters in the context of chromatin.
引用
收藏
页码:3020 / 3031
页数:12
相关论文
共 66 条
[1]   ACTIVATION OF CAMP AND MITOGEN RESPONSIVE GENES RELIES ON A COMMON NUCLEAR FACTOR [J].
ARIAS, J ;
ALBERTS, AS ;
BRINDLE, P ;
CLARET, FX ;
SMEAL, T ;
KARIN, M ;
FERAMISCO, J ;
MONTMINY, M .
NATURE, 1994, 370 (6486) :226-229
[2]   Promoter selective transcriptional synergy mediated by sterol regulatory element binding protein and Sp1: A critical role for the btd domain of Sp1 [J].
Athanikar, JN ;
Sanchez, HB ;
Osborne, TF .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (09) :5193-5200
[3]   The CBP co-activator is a histone acetyltransferase [J].
Bannister, AJ ;
Kouzarides, T .
NATURE, 1996, 384 (6610) :641-643
[4]   CBP-INDUCED STIMULATION OF C-FOS ACTIVITY IS ABROGATED BY E1A [J].
BANNISTER, AJ ;
KOUZARIDES, T .
EMBO JOURNAL, 1995, 14 (19) :4758-4762
[5]  
Bannister AJ, 1995, ONCOGENE, V11, P2509
[6]  
BRIGGS MR, 1993, J BIOL CHEM, V268, P14490
[7]   The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].
Brown, MS ;
Goldstein, JL .
CELL, 1997, 89 (03) :331-340
[8]   RSC, an essential, abundant chromatin-remodeling complex [J].
Cairns, BR ;
Lorch, Y ;
Li, Y ;
Zhang, MC ;
Lacomis, L ;
ErdjumentBromage, H ;
Tempst, P ;
Du, J ;
Laurent, B ;
Kornberg, RD .
CELL, 1996, 87 (07) :1249-1260
[9]   Role of CBP/P300 in nuclear receptor signalling [J].
Chakravarti, D ;
LaMorte, VJ ;
Nelson, MC ;
Nakajima, T ;
Schulman, IG ;
Juguilon, H ;
Montminy, M ;
Evans, RM .
NATURE, 1996, 383 (6595) :99-103
[10]   ASSEMBLY OF RECOMBINANT TFIID REVEALS DIFFERENTIAL COACTIVATOR REQUIREMENTS FOR DISTINCT TRANSCRIPTIONAL ACTIVATORS [J].
CHEN, JL ;
ATTARDI, LD ;
VERRIJZER, CP ;
YOKOMORI, K ;
TJIAN, R .
CELL, 1994, 79 (01) :93-105