Corepressors (NCoR and SMRT) as well as coactivators are recruited to positively regulated 1α,25-dihydroxyvitamin D3-responsive genes.
Corepressors (NCoR and SMRT) as well as coactivators are recruited to positively regulated 1α,25-dihydroxyvitamin D3-responsive genes.
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DOI：
10.1016/j.jsbmb.2012.08.006
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发表时间：
2013-07
影响因子：
4.1
通讯作者：
Pike, J. Wesley
中科院分区：
文献类型：
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作者：
Meyer, Mark B.;Pike, J. Wesley
转录因子需要辅激活子和辅阻遏子来调节哺乳动物细胞中的转录。维生素D受体（VDR）利用辅激活子和辅抑制子来严格控制各种基因的活性，这些基因可以调节钙转运，减缓增殖并促进免疫反应。我们最近在人结肠癌细胞中建立了VDR/RXR顺式组，并将这些结合位点与受1α，25-二羟基维生素D3（1，25（OH）2D 3）调节的基因连接起来。在本文所述的其他研究中，我们证明了共激活因子SRC 1，CBP和MED 1被募集到上调的基因中，以促进预期的转录。SRC 1与VDR/RXR结合的相关性最高（50%）。然而，我们也发现辅阻遏物分子如NCoR和SMRT与SRC 1、CBP或MED 1一起沿着存在于这些1，25（OH）2D 3激活的基因增强子上。有趣的是，全基因组NCoR结合通过响应于1，25（OH）2D 3处理增加其与VDR结合的关联来模拟VDR结合。总的来说，这些数据表明，辅阻遏物和辅激活物复合物在激活或主动阻遏1，25（OH）2D 3反应基因中的复杂作用。
Transcription factors require coactivators and corepressors to modulate transcription in mammalian cells. The vitamin D receptor (VDR) utilizes coactivators and corepressors to gain tight control over the activity of a diverse set of genes that can regulate calcium transport, slow proliferation and promote immune responses. We have recently established the VDR/RXR cistrome in human colon cancer cells and have linked these binding sites to the genes that are regulated by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In additional studies described herein, we demonstrate that the coactivators SRC1, CBP and MED1 are recruited to upregulated genes to facilitate transcription as expected. SRC1 was the most highly correlated to VDR/RXR binding (50%). However, we also found that corepressor molecules such as NCoR and SMRT were present along with SRC1, CBP or MED1 at these 1,25(OH)2D3 activated gene enhancers. Interestingly, genome-wide NCoR binding mimicked VDR binding by increasing its association with VDR binding in response to 1,25(OH)2D3 treatment. Overall, these data indicate a complex role for corepressor and coactivator complexes in the activation or active repression of 1,25(OH)2D3 responsive genes.
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影响因子：
--
作者：
Meyer, Mark B.;Goetsch, Paul D.;Pike, J. Wesley
通讯作者：
Pike, J. Wesley
影响因子：
64.5
作者：
KLEINHITPASS, L;TSAI, SY;OMALLEY, BW
通讯作者：
OMALLEY, BW
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
--
作者：
Zella, Lee A.;Kim, Sungtae;Pike, J. Wesley
通讯作者：
Pike, J. Wesley
影响因子：
10.5
作者：
Nielsen, Ronni;Pedersen, Thomas Askov;Stunnenberg, Hendrik G.
通讯作者：
Stunnenberg, Hendrik G.