SRC-p300 coactivator complex is required for thyroid hormone-induced amphibian metamorphosis.

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摘要：

Gene activation by the thyroid hormone (T3) receptor (TR) involves the recruitment of specific coactivator complexes to T3-responsive promoters. A large number of coactivators for TR have been isolated and characterized . However, their roles and functions during development have remained largely unknown. We have utilized metamorphosis in to study the role of these coactivators during post-embryonic development. Metamorphosis is totally dependent on the thyroid hormone, and TR mediates a vast majority, if not all, of the developmental effects of the hormone. We have previously shown that TR recruits the coactivator SRC3 (teroid eceptor oactivator-) and that coactivator recruitment is essential for metamorphosis. To determine whether SRCs are indeed required, we have analyzed the role of the histone acetyltransferase p300/CREB-binding protein (CBP), which was reported to be a component of the SRC·coactivator complexes. Chromatin immunoprecipitation revealed that p300 is recruited to T3-responsive promoters, implicating a role of p300 in TR function. Further, transgenic tadpoles overexpressing a dominant negative form of p300, F-dnp300, containing only the SRC-interacting domain, displayed arrested or delayed metamorphosis. Molecular analyses of the transgenic F-dnp300 animals showed that F-dnp300 was recruited by TR (displacing endogenous p300) and inhibited the expression of T3-responsive genes. Our results thus suggest that p300 and/or its related CBP is an essential component of the TR-signaling pathway and support the notion that p300/CBP and SRC proteins are part of the same coactivator complex during post-embryonic development.

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关键词：

SRCp Coactivator Required Hormoneinduced Amphibian Metamorphosis

DOI：

10.1074/jbc.M607589200

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年份：

2007