确定增强子（可与调控蛋白结合来增强基因转录水平的短DNA片段）的时空分布，在人类基因组的功能注解方面仍是一个挑战。ChIP-seq（英文全称为“chromatin immunoprecipitation with massively parallel sequencing”）的活体应用被用来描绘在发育中的小鼠组织中与增强子相关的蛋白p300在整个基因组范围的分布。在胚胎前脑、中脑和四肢组织中，有几千个p300结合点，对其中的一个样本所做测试表明，它们大多数都与可重现的增强子活性有关。这种类型的数据集对于研究增强子在人体生物学及病理过程中的作用将是有用的。（生物谷Bioon.com）
中国第一ChIP论坛：ChIP Forum
生物谷推荐原始出处：
Nature 457, 854-858 (12 February 2009) | doi:10.1038/nature07730
ChIP-seq accurately predicts tissue-specific activity of enhancers
Axel Visel1,4, Matthew J. Blow1,2,4, Zirong Li3, Tao Zhang2, Jennifer A. Akiyama1, Amy Holt1, Ingrid Plajzer-Frick1, Malak Shoukry1, Crystal Wright2, Feng Chen2, Veena Afzal1, Bing Ren3, Edward M. Rubin1,2 & Len A. Pennacchio1,2
1 Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
2 US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA
3 Ludwig Institute for Cancer Research, University of California San Diego (UCSD) School of Medicine, La Jolla, California 92093, USA
4 These authors contributed equally to this work.
A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.
