確定增強子（可與調控蛋白結合來增強基因轉錄水平的短DNA片段）的時空分布,，在人類基因組的功能注解方面仍是一個挑戰(zhàn)。ChIP-seq（英文全稱為“chromatin immunoprecipitation with massively parallel sequencing”）的活體應用被用來描繪在發(fā)育中的小鼠組織中與增強子相關的蛋白p300在整個基因組范圍的分布,。在胚胎前腦,、中腦和四肢組織中，有幾千個p300結合點,，對其中的一個樣本所做測試表明,，它們大多數(shù)都與可重現(xiàn)的增強子活性有關。這種類型的數(shù)據(jù)集對于研究增強子在人體生物學及病理過程中的作用將是有用的,。（生物谷Bioon.com）
中國第一ChIP論壇：ChIP Forum
生物谷推薦原始出處：
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.
