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从 CCAAT 盒看启动子结构

A perspective of promoter architecture from the CCAAT box.

机构信息

Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milano, Italy.

出版信息

Cell Cycle. 2009 Dec 15;8(24):4127-37. doi: 10.4161/cc.8.24.10240. Epub 2009 Dec 5.

DOI:10.4161/cc.8.24.10240
PMID:19946211
Abstract

The CCAAT box is an important promoter element regulated by NF-Y, a conserved trimer with histone-like features. We describe a new Position Specific Frequency Matrix (PSFM): we derived from 328 NF-Y promoters from the literature the p-CCAAT, and refined it by analysing ChIP on chip data (g-CCAAT). Interestingly, g-CCAAT has distinct features, such as variations within the CCAAT pentanucleotide. We validated the NF-Y-dependency of several promoters with functional assays. We examined the presence of these PSFMs in all human promoters and detail a number of parameters of CCAAT boxes: position, orientation, distance from TSS, presence of TATA, CpG islands and enrichments of nearby TF elements. The CCAAT genes fall into different GO categories, with cell cycle and chromatin/transcription specifically enriched. Additional findings surfaced: (1) the CCAAT-TATA combination, often mentioned in textbooks, is an exception, rather than the rule. CCAAT promoters are less precise in terms of TSS; (2) There is a good correlation between CCAAT and CpG islands; (3) selective TFs sites are enriched in CCAAT promoters, with precise stereoalignements of some of them. In conclusion, the new features of the CCAAT box and the link with the neighbouring elements will help in the functional classification of promoters.

摘要

CCAAT 框是一个重要的启动子元件,受 NF-Y 调节,NF-Y 是一种具有组蛋白样特征的保守三聚体。我们描述了一种新的位置特异性频率矩阵 (PSFM):我们从文献中的 328 个 NF-Y 启动子中推导出 p-CCAAT,并通过分析芯片上的 ChIP 数据 (g-CCAAT) 对其进行了改进。有趣的是,g-CCAAT 具有独特的特征,例如在 CCAAT 五核苷酸内的变化。我们通过功能测定验证了几个启动子的 NF-Y 依赖性。我们检查了这些 PSFMs 在所有人类启动子中的存在情况,并详细介绍了 CCAAT 盒的一些参数:位置、方向、与 TSS 的距离、TATA 的存在、CpG 岛以及附近 TF 元素的富集。CCAAT 基因分为不同的 GO 类别,细胞周期和染色质/转录特别丰富。还发现了一些其他发现:(1)CCAAT-TATA 组合,在教科书中经常提到,是一个例外,而不是规则。CCAAT 启动子在 TSS 方面的精度较低;(2)CCAAT 与 CpG 岛之间存在良好的相关性;(3)CCAAT 启动子中富含选择性 TF 结合位点,其中一些具有精确的立体定向排列。总之,CCAAT 框的新特征及其与邻近元件的联系将有助于启动子的功能分类。

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