Review

Next-generation sequencing is poised to unleash dramatic changes in every area of molecular biology. In the past few years, chromatin immunoprecipitation (ChIP) on tiled microarrays (ChIP-chip) has been an important tool for genome-wide mapping of DNA-binding proteins or histone modifications. Now, ChIP followed by direct sequencing of DNA fragments (ChIP-seq) offers superior data with less noise and higher resolution and is likely to replace ChIP-chip in the near future. We will describe advantages of this new technology and outline some of the issues in dealing with the data. ChIP-seq generates considerably larger quantities of data and the most challenging aspect for investigators will be computational and statistical analysis necessary to uncover biological insights hidden in the data.

Copy-number variation (CNV) is a major class of genomic variation with potentially important functional consequences in both normal and diseased populations. Remarkable advances in development of next-generation sequencing (NGS) platforms provide an unprecedented opportunity for accurate, high-resolution characterization of CNVs. In this unit, we give an overview of available computational tools for detection of CNVs and discuss comparative advantages and disadvantages of different approaches.

A transcriptional regulatory network represents a molecular framework in which developmental or environmental cues are transformed into differential expression of genes. Transcriptional regulation is mediated by the combinatorial interplay between cis-regulatory DNA elements and trans-acting transcription factors, and is perhaps the most important mechanism for controlling gene expression. Recent innovations, most notably the method for detecting protein-DNA interactions genome-wide, can help provide a comprehensive catalog of cis-regulatory elements and their interaction with given trans-acting factors in a given condition. A transcriptional regulatory network that integrates such information can lead to a systems-level understanding of regulatory mechanisms. In this review, we will highlight the key aspects of current knowledge on eukaryotic transcriptional regulation, especially on known transcription factors and their interacting regulatory elements. Then we will review some recent technical advances for genome-wide mapping of DNA-protein interactions based on high-throughput sequencing. Finally, we will discuss the types of biological insights that can be obtained from a network-level understanding of transcription regulation as well as future challenges in the field.