The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein
The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein
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DOI：
10.1042/bj20090134
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发表时间：
2009-09-15
影响因子：
4.1
通讯作者：
Kao, Kenneth R.
中科院分区：
文献类型：
--
作者：
Andrews, Phillip G. P.;He, Zhijian;Kao, Kenneth R.
Pygopus是表达规范的Wnt靶基因所需的β-连环蛋白/T细胞因子(T细胞因子)转录激活复合体的核心成分。最近的证据表明，Pygopus可以解释与靶基因相关的组蛋白甲基化，并且它被证明是组蛋白乙酰化所必需的。然而，一种特定的乙酰转移酶的参与还没有确定。在这篇报道中，我们证明了Pygopus可以与HAT(组蛋白乙酰转移酶)CBP[CREB(cAMP反应元件结合蛋白)结合蛋白]相互作用。这种相互作用是通过Pygopus的NHD(N-末端同源结构域)实现的，它与CBP HAT结构域附近的两个区域结合。在HEK-293(人胚胎肾293)细胞中，转基因的hPygo2(人Pygopus2)和CBP蛋白与内源性hPygo2和CBP蛋白共沉淀，在SW480结直肠癌细胞中两种蛋白共定位。与CBP的相互作用也增强了Pygopus的DNA拴系和TCF/LEF1(淋巴增强因子1)依赖的转录活性。此外，免疫沉淀的Pygopus蛋白复合体显示了CBP依赖的组蛋白乙酰转移酶活性。我们的数据支持一个模型，在该模型中，Pygopus的NHD区域需要通过包括转录激活和组蛋白乙酰化的机制来增强TCF/β-catenin介导的转录激活，组蛋白乙酰化是由CBP组蛋白乙酰转移酶招募引起的。
Pygopus is a core component of the beta-catenin/TCF (T-cell factor) transcriptional activation complex required for the expression of canonical Wnt target genes. Recent evidence suggests that Pygopus could interpret histone methylation associated with target genes and it was shown to be required for histone acetylation. The involvement of a specific acetyltransferase, however, was not determined. In this report, we demonstrate that Pygopus can interact with the HAT (histone acetyltransferase) CBP [CREB (cAMP-responsive-element-binding protein)-binding protein]. The interaction is via the NHD (N-terminal homology domain) of Pygopus, which binds to two regions in the vicinity of the HAT domain of CBP. Transfected and endogenous hPygo2 (human Pygopus2) and CBP proteins co-immunoprecipitate in HEK-293 (human embryonic kidney 293) cells and both proteins co-localize in SW480 colorectal cancer cells. The interaction with CBP also enhances both DNA-tethered and TCF/LEF1 (lymphoid enhancing factor 1)-dependent transcriptional activity of Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the NHD region of Pygopus is required to augment TCF/beta-catenin-mediated transcriptional activation by a mechanism that includes both transcriptional activation and histone acetylation resulting from the recruitment of the CBP histone acetyltransferase.