期刊
NUCLEIC ACIDS RESEARCH
卷 38, 期 16, 页码 5456-5471出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq286
关键词
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资金
- MOEHRD, Republic of Korea [KRF-2007-313-C00594]
- Ministry of Health and Welfare, Republic of Korea [02-PJ10-PG8-EC01-0012]
- Brain Korea 21 Project
- MOEHRD, through the Research Team for Mammalian Development and Differentiation
- Hanyang University
Data presented here extends our previous observations on alpha-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous alpha-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In vitro, recombinant CP2c, CP2b and PIAS1 bound DNA as a stable CBP (CP2c/CP2b/PIAS1) complex. Following PIAS1 knockdown in MEL cells, however, the association of endogenous CP2c and CP2b with the alpha-globin promoter simultaneously decreased. By mapping the CP2b- and CP2c-binding domains on PIAS1, and the PIAS1-binding domains on CP2b and CP2c, we found that two regions of PIAS1 that interact with CP2c/CP2b are required for its co-activator function. We propose that CP2c, CP2b, and PIAS1 form a hexametric complex with two units each of CP2c, CP2b, and PIAS1, in which PIAS1 serves as a clamp between two CP2 proteins, while CP2c binds directly to the target DNA and CP2b mediates strong transactivation.
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