The human genome is predominantly composed of nonprotein-coding sequences whose function remains largely undefined. A significant portion of the noncoding DNA is believed to serve as transcriptional regulatory elements that control gene expression in specific cell types at appropriate developmental stages. Identifying these regulatory sequences and determining the mechanisms by which they act present a great challenge in the postgenomic era. Previous investigations using genetic, molecular, and biochemical approaches have uncovered a large number of proteins involved in regulating transcription. Knowledge of the genomic locations of DNA binding for these proteins in the nucleus should define the identity and nature of the transcriptional regulatory sequences and reveal the gene regulatory networks in cells. Chromatin immunoprecipitation (ChIP) is a common method for detecting interactions between a protein and a DNA sequence in vivo. In recent years, this method has been combined with DNA microarrays and other high-throughput technologies to enable genome-wide identification of DNA-binding sites for various nuclear proteins. Here, we review recent advances in ChIP-based methods for genome-wide detection of protein-DNA interactions, and discuss their significance in enhancing our knowledge of the gene regulatory networks and epigenetic mechanisms in cells.

中文翻译：

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蛋白质-DNA相互作用的全基因组分析。

人类基因组主要由非蛋白质编码序列组成，其功能在很大程度上尚未定义。据信非编码DNA的很大一部分充当转录调节元件，其在适当的发育阶段控制特定细胞类型中的基因表达。在后基因组时代，鉴定这些调控序列并确定它们起作用的机制是一个巨大的挑战。以前使用遗传，分子和生化方法进行的研究已经发现了许多调控转录的蛋白质。对这些蛋白质在细胞核中结合的DNA的基因组位置的了解应该定义转录调控序列的身份和性质，并揭示细胞中的基因调控网络。染色质免疫沉淀（ChIP）是在体内检测蛋白质和DNA序列之间相互作用的常用方法。近年来，该方法已与DNA微阵列和其他高通量技术相结合，可在全基因组范围内鉴定各种核蛋白的DNA结合位点。在这里，我们回顾了基于ChIP的蛋白质-DNA相互作用的全基因组检测方法的最新进展，并讨论了它们在增强我们对细胞中基因调控网络和表观遗传机制的认识方面的意义。