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
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