Methods 48 (2009) 217
Contents lists available at ScienceDirect
Methods journal homepage: www.elsevier.com/locate/ymeth
Guest Editor’s Introduction
Global approaches to study gene regulation
Genome-wide approaches provide a powerful global view of biological processes, thus complementing more traditional reductionist approaches. Global studies are driven to a large extent by available methods and technologies, which are rapidly evolving to provide ever deeper insight into genome regulation. The recent explosion in applications of next-generation sequencing methods is just the latest example of the breathtaking progress being made in this field. This issue of the Methods journal brings together articles from experts and pioneers who present a wide range of stateof-the-art approaches to study gene regulation, including global analyses of chromatin, transcription, RNA, translation, proteins, and computational methods. The genomic organisation of chromatin has large implications for gene regulation and beyond. Multiple methods are now available to sample chromatin patterns. Ekwall and colleagues describe an approach for global mapping of nucleosomes applied to fission yeast [1]. Meissner and colleagues report a method to analyse global DNA methylation using a next-generation bisulfite sequencing approach [2]. Giresi and Lieb present the FAIRE approach to identify nucleosome-free regulatory regions within genomes [3]. Other methods can give direct insight into transcriptional processes. ChIP-seq is emerging as a highly popular approach to interrogate genomic binding sites of regulatory proteins, and this method is introduced by Hadfield, Odom and colleagues [4]. Landry and Wilhelm [5] describe another recent application of nextgeneration sequencing, RNA-seq, which is bound to supersede microarray-based expression profiling. Andrews and colleagues report a clever functional genomics approach to identify new transcriptional regulators, combining powerful yeast genetics, arraybased reagents, and high-throughput imaging [6]. Computational approaches are critical to mine genome-wide data sets, which often presents considerable challenges. Beyer and colleagues survey methods for detecting and analysing eQTLs, which are providing valuable insight into the relationships between genotype and transcripton [7], while Babu and colleagues survey methods to reconstruct transcriptional regulatory networks from genomic data [8]. Important regulatory processes take place at post-transcriptional levels as well, which are also amenable to global analyses. Transcripts associate with different combinations of RNA-binding proteins, and the CLIP method combined with next-generation sequencing can identify the interaction sites between proteins
1046-2023/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.ymeth.2009.06.006
and RNAs as described by Ule and colleagues [9]. The PASTA method presented by Beilharz and Preiss [10] allows for comprehensive measurements of polyadenylation, which influences the fate of many RNAs. Another important regulatory level takes place during translation, with RNAs being translated at different efficiencies. Arava and colleagues describe a method that combines polysome profiling with microarrays to determine ribosome association of RNAs [11], while Gerber and colleagues report a recently developed approach, termed RAP, to sample all RNAs associated with purified ribosomes [12]. Ultimately, it will also be important to globally analyse proteins, and this issue concludes with an article by Wolf and colleagues introducing a comprehensive proteomic method used for protein profiling in fission yeast [13]. I thank all authors for their helpful contributions. References [1] Alexandra Lantermann, Annelie Strålfors, Fredrik Fagerström-Billai, Philipp Korber, Karl Ekwall, Methods 48 (2009) 218–225. [2] Zachary D. Smith, Hongcang Gu, Christoph Bock, Andreas Gnirke, Alexander Meissner, Methods 48 (2009) 226–232. [3] Paul G. Giresi, Jason D. Lieb, Methods 48 (2009) 233–239. [4] Dominic Schmidt, Michael D. Wilson, Christiana Spyrou, Gordon D. Brown, James Hadfield, Duncan T. Odom, Methods 48 (2009) 240–248. [5] Brian T. Wilhelm, Josette-Renée Landry, Methods 48 (2009) 249–257. [6] Pinay Kainth, Holly Elizabeth Sassi, Lourdes Peña-Castillo, Gordon Chua, Timothy R. Hughes, Brenda Andrews, Methods 48 (2009) 258–264. [7] Jacob J. Michaelson, Salvatore Loguercio, Andreas Beyer, Methods 48 (2009) 265–276. [8] Rekin’s Janky, Jacques van Helden, M. Madan Babu, Methods 48 (2009) 277– 286. [9] Zhen Wang, James Tollervey, Michael Briese, Daniel Turner, Jernej Ule, Methods 48 (2009) 287–293. [10] Traude H. Beilharz, Thomas Preiss, Methods 48 (2009) 294–300. [11] Daniel Melamed, Erez Eliyahu, Yoav Arava, Methods 48 (2009) 301–305. [12] Regula E. Halbeisen, Tanja Scherrer, André P. Gerber, Methods 48 (2009) 306– 310. [13] Laurence M. Brill, Khatereh Motamedchaboki, Shuangding Wu, Dieter A. Wolf, Methods 48 (2009) 311–319.
Jürg Bähler Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, Gower Street, Darwin Building, London WC1E 6BT, UK E-mail address:
[email protected]