Schübeler, D.

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Foreword: From genetic diversity to chromosomal biology: an array of tasksbeyond expressionDNA sequencing is revealing the completegenetic information of an increasing number oforganisms. Sequencing programmes are provid-ing comprehensive catalogues of protein codinggenes and genome databases are now commonand invaluable tools for biological research. Atthe same time it is also evident that sequenceinformation alone is insufﬁcient for understand-ing the process of gene regulation and genomepropagation. While this might reﬂect in part ourlimited knowledge of cellular regulation, it high-lights the need to obtain more information onhow the genome is interpreted in a living cell. Istranscription limited to protein coding genes?What speciﬁes transcription factor binding? Howis DNA replication regulated? How are theseevents modulated by epigenetic modiﬁcations ofDNA and chromatin?None of the above questions is new to chromo-some biology but thus far they have mostly beentackled by analyzing single gene loci in greatdetail. The development of DNA microarrays asminiaturized slot blots has enabled researchers tomeasure thousands of sequence probes in oneexperiment and thus to perform large-scale andunbiased analyses. Di¡erent experimental plat-forms for arrays exist, most of which have beendriven by a need to pro¢le gene expression in orderto identify di¡erentially regulated genes. Indeedglobal expression analyses have moved in a veryshort time from high technologies that were onlyavailable in a handful of laboratories to a standardanalysis tool in biological research.Only very recently has microarray technologybeen used beyond expression pro¢ling to gain insi-ghts into features of chromosomal DNA, such asprotein binding or genetic variation. Exciting newapproaches have been developed to measure thephysiology of chromosomes in unprecedenteddetail.The rapid progress in this ¢eld led the EditorialBoard of Chromosome Research to propose aspecial issue with a focus on genomic microarrays.The goal was to cover many di¡erent biologicalquestions that can be addressed with this exp-erimental tool as well as to introduce the di¡erenttechnical approaches. The resulting volumecombines up-to-date reviews including originalresearch from leading groups in the ¢eld.ClaireKidgell and ElizabethWinzeler discuss howgenetic diversity at the nucleotide level can be ana-lyzed on oligonucleotide microarrays and how thisinformation can be used in comparative genomics,polymorphism discovery and genotyping. Wan Lamet al. report how comparative genomic hybridiza-tion is applied to determine genomic instability incancer, while Heike Fiedler et al. introduce howhuman genomic microarrays can be used to measurechromatin structure andDNAreplication.One surprising observation that was only madepossible through the use of tiled chromosomalarrays was the high abundance of transcription out-side of open reading frames. Mike Snyder et al. dis-cuss how high-resolution tiling arrays are used toidentify transcriptional activity outside predictedcoding genes and how these observations challengemuch of our thinking on regulation of transcrip-tion. Identifying sites of transcription factor bind-ing presents another major task in decipheringgene regulation. Alexandre Blais and BrianDynlacht discuss how this question can be addres-sed with microarrays representing gene promotersand they also introduce the problems and pitfallsin interpreting the resulting datasets. Modi¢ca-tions of DNA and bound chromatin present keyepigenetic modulators of genetic readouts. MartinLode¤ n and Bas van Steensel discuss di¡erentexperimental approaches to determine higherorder chromatin structure using genomic tools,while Vincent Colot et al. review the ways inwhich epigenomic approaches have shed light onchromosomal regulation in plants. Our knowledgeof DNA duplication has bene¢ted from recentgenome-wide analyses of replication initiation andtiming. In this issue David MacAlpine and StephenBell summarize these e¡orts and, furthermore,Chromosome Research 13: 223–224, 2005. 223# 2005 Springer. Printed in the Netherlandsthey reanalyze some of the published data. Thatgenome-wide measures can also identify post-transcriptional regulation is nicely illustrated byJack Keene and Patrick Lager, who propose anintrinsic model of post-transcriptional operonsbased on global interaction networks of RNAbinding proteins with target mRNAs.I am grateful that leading scientists have agreedto contribute to this issue and I thank WendyBickmore for initiating the project and HerbertMacgregor for his enthusiasm and encouragementthroughout its development. I also acknowledgethe support of Nimblegen in covering the cost ofthe cover picture of this issue of ChromosomeResearch.Dirk Schˇbeler (Guest Editor)Friedrich-Miescher-Institutefor Biomedical ResearchBaselSwitzerland224 Foreword

Foreword: From genetic diversity to chromosomal biology: an array of tasks beyond expression

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Foreword: From genetic diversity to chromosomal biology: an array of tasks beyond expression

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