期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 23, 期 9, 页码 3339-3351出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.23.9.3339-3351.2003
关键词
-
资金
- FIC NIH HHS [R03 TW000990, TW00990] Funding Source: Medline
- NIAMS NIH HHS [R01 AR049069, AR48818, P01 AR048818] Funding Source: Medline
- NIDCR NIH HHS [DE12528, R37 DE012528, R01 DE012528] Funding Source: Medline
p300 is a multifunctional transcriptional coactivator that serves as an adapter for several transcription factors including nuclear steroid hormone receptors. p300 possesses an intrinsic histone acetyltransferase (HAT) activity that may be critical for promoting steroid-dependent transcriptional activation. In osteoblastic cells, transcription of the bone-specific osteocalcin (OC) gene is principally regulated by the Runx2/Cbfa1 transcription factor and is stimulated in response to vitamin D-3 via the vitamin D-3 receptor complex. Therefore, we addressed p300 control of basal and vitamin D-3-enhanced activity of the OC promoter. We find that transient overexpression of p300 results in a significant dose-dependent increase of both basal and vitamin D-3-stimulated OC gene activity. This stimulatory effect requires intact Runx2/Cbfa1 binding sites and the vitamin D-responsive element. In addition, by coimmunoprecipitation, we show that the endogenous Runx2/Cbfa1 and p300 proteins are components of the same complexes within osteoblastic cells under physiological concentrations. We also demonstrate by chromatin immunoprecipitation assays that p300, Runx2/Cbfa1, and 1alpha,25-dihydroxyvitamin D-3 receptor interact with the OC promoter in intact osteoblastic cells expressing this gene. The effect of p300 on the OC promoter is independent of its intrinsic HAT activity, as a HAT-deficient p300 mutant protein up-regulates expression and cooperates with P/CAF to the same extent as the wild-type p3OO. On the basis of these results, we propose that p300 interacts with key transcriptional regulators of the OC gene and bridges distal and proximal OC promoter sequences to facilitate responsiveness to vitamin D-3.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据