Hot off the presses! Feb 01 Nat Rev Genet

The Feb 01 issue of the Nat Rev Genet is now up on Pubget (About Nat Rev Genet): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Gene regulation: Resolving transcription factor binding | PDF (415 KB)
  - Nat Rev Genet 13(2):71 (2012)
  The binding of transcription factors to DNA in vivo is a highly regulated process. Through the refinement of techniques for identifying in vivo binding sites or in vitro binding affinities, three studies have now improved our understanding of the regulation of transcription factor binding both by DNA sequence and by cofactor interactions.
• Synthetic biology: Simplifying design | PDF (281 KB)
  - Nat Rev Genet 13(2):72 (2012)
  Synthetic biological devices hold great potential for many biotechnological applications. However, the functional complexity of synthetic devices has been limited by the available design tools.
• Differentiation: Racing to decide | PDF (279 KB)
  - Nat Rev Genet 13(2):72 (2012)
  Cells that can differentiate towards one fate or another occur across species. However, understanding how an individual cell 'chooses' its fate is challenging; cross-regulation between competing programs has been suggested as a mechanism, but recent work in bacteria shows that fate can depend on which program wins a molecular race.
• RNA stability: Remember your driver | PDF (146 KB)
  - Nat Rev Genet 13(2):72 (2012)
  The stability of mRNA is often assumed to be dictated by a transcript's sequence features. Two new studies highlight that mRNA stability can be influenced by a memory of the promoter from which expression of the transcript was driven.
• Gene expression: Genetic support network to the rescue | PDF (298 KB)
  - Nat Rev Genet 13(2):74 (2012)
  Although great strides have been made in determining individual genotypes, this progress is not matched by a clearer picture of how phenotype follows from genotype. A study in Caenorhabditis elegans now shows that the phenotypic consequences of inherited mutations can be accurately predicted by considering variation between individuals in their compensatory responses to the mutation.
• Small RNAs: Little transgressions | PDF (141 KB)
  - Nat Rev Genet 13(2):75 (2012)
  The molecular basis of transgressive segregation — which causes phenotypes of a hybrid to lie outside the range of the parental phenotypes — has been debated for decades. A new study in tomato plants indicates that transgressive phenotypes are mediated by the silencing of novel targets by small RNAs (sRNAs), which leads to genome-wide epigenetic and gene-expression changes in the hybrid.
• Epigenetics: Dynamic DNA methylation | PDF (329 KB)
  - Nat Rev Genet 13(2):75 (2012)
  DNA methylation is an important epigenetic modification, although the regulation of its deposition is not well-understood. Furthermore, our current understanding is mostly limited to CpG methylation; methylation can also occur at cytosines in other contexts.
• Mutation: Linking transcription and genome instability | PDF (100 KB)
  - Nat Rev Genet 13(2):73 (2012)
  Two papers reveal details of how transcription can jeopardize genome integrity. Helmrich et al.
• 
  - Nat Rev Genet 13(2):73 (2012)
  
• 
  - Nat Rev Genet 13(2):73 (2012)
  
• 
  - Nat Rev Genet 13(2):73 (2012)
  
• 
  - Nat Rev Genet 13(2):74 (2012)
  
• 
  - Nat Rev Genet 13(2):74 (2012)
  
• 
  - Nat Rev Genet 13(2):74 (2012)
  
• 
  - Nat Rev Genet 13(2):74 (2012)
  
• Proteinâ€"RNA interactions: new genomic technologies and perspectives
  - Nat Rev Genet 13(2):77 (2012)
  RNA-binding proteins are key players in the regulation of gene expression. In this Progress article, we discuss state-of-the-art technologies that can be used to study individual RNA-binding proteins or large complexes such as the ribosome. We also describe how these approaches can be used to study interactions with different types of RNAs, including nascent transcripts, mRNAs, microRNAs and ribosomal RNAs, in order to investigate transcription, RNA processing and translation. Finally, we highlight current challenges in data analysis and the future steps that are needed to obtain a quantitative and high-resolution picture of protein–RNA interactions on a genome-wide scale.
• Crop genomics: advances and applications
  - Nat Rev Genet 13(2):85 (2012)
  The completion of reference genome sequences for many important crops and the ability to perform high-throughput resequencing are providing opportunities for improving our understanding of the history of plant domestication and to accelerate crop improvement. Crop plant comparative genomics is being transformed by these data and a new generation of experimental and computational approaches. The future of crop improvement will be centred on comparisons of individual plant genomes, and some of the best opportunities may lie in using combinations of new genetic mapping strategies and evolutionary analyses to direct and optimize the discovery and use of genetic variation. Here we review such strategies and insights that are emerging.
• Epigenetics and the environment: emerging patterns and implications
  - Nat Rev Genet 13(2):97 (2012)
  Epigenetic phenomena in animals and plants are mediated by DNA methylation and stable chromatin modifications. There has been considerable interest in whether environmental factors modulate the establishment and maintenance of epigenetic modifications, and could thereby influence gene expression and phenotype. Chemical pollutants, dietary components, temperature changes and other external stresses can indeed have long-lasting effects on development, metabolism and health, sometimes even in subsequent generations. Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems. These have implications for structuring future research and understanding disease and development.
• Computer simulations: tools for population and evolutionary genetics
  - Nat Rev Genet 13(2):110 (2012)
  Computer simulations are excellent tools for understanding the evolutionary and genetic consequences of complex processes whose interactions cannot be analytically predicted. Simulations have traditionally been used in population genetics by a fairly small community with programming expertise, but the recent availability of dozens of sophisticated, customizable software packages for simulation now makes simulation an accessible option for researchers in many fields. The in silico genetic data produced by simulations, along with greater availability of population-genomics data, are transforming genetic epidemiology, anthropology, evolutionary and population genetics and conservation. In this Review of the state-of-the-art of simulation software, we identify applications of simulations, evaluate simulator capabilities, provide a guide for their use and summarize future directions.
• Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription
  - Nat Rev Genet 13(2):123 (2012)
  Dosage compensation is an epigenetic mechanism that normalizes gene expression from unequal copy numbers of sex chromosomes. Different organisms have evolved alternative molecular solutions to this task. In Drosophila melanogaster, transcription of the single male X chromosome is upregulated by twofold in a process orchestrated by the dosage compensation complex. Despite this conceptual simplicity, dosage compensation involves multiple coordinated steps to recognize and activate the entire X chromosome. We are only beginning to understand the intriguing interplay between multiple levels of local and long-range chromatin regulation required for the fine-tuned transcriptional activation of a heterogeneous gene population. This Review highlights the known facts and open questions of dosage compensation in D. melanogaster.
• Rare and common variants: twenty arguments
  - Nat Rev Genet 13(2):135 (2012)
  Genome-wide association studies have greatly improved our understanding of the genetic basis of disease risk. The fact that they tend not to identify more than a fraction of the specific causal loci has led to divergence of opinion over whether most of the variance is hidden as numerous rare variants of large effect or as common variants of very small effect. Here I review 20 arguments for and against each of these models of the genetic basis of complex traits and conclude that both classes of effect can be readily reconciled.
• Correspondence: Familial risks in understanding type 1 diabetes genetics
  - Nat Rev Genet 13(2):146 (2012)
  There have been impressive advances in the genetics of type 1 diabetes (T1D) that are increasingly being translated into a greater understanding of the disease mechanisms, as reviewed in this journal by Polychronakos and Li (Understanding type 1 diabetes through genetics: advances and prospects. Nature Reviews Genetics12, 781–792)1.
• Correspondence: Europe and direct-to-consumer genetic tests
  - Nat Rev Genet 13(2):146 (2012)
  In a recent Ethics watch article in this journal (Ethics watch: Direct-access genetic testing: the view from Europe. Nature Reviews Genetics12, 670 (2011))1, a call for a more detailed investigation of direct-to-consumer (DTC) genetic testing in Europe was made in order to enable enforcement of a more targeted European regulation.
• Repetitive DNA and next-generation sequencing: computational challenges and solutions
  - Nat Rev Genet 13(2):146 (2012)
  Nature Reviews Genetics13, 36–46 (2012) In the above article, Table 1 provided a URL for software called 'SNiPer'. This should have been a URL for software called 'Sniper'. The correct URL (http://kim.bio.upenn.edu/software/sniper.shtml) has been inserted, and in Table 1 and in the two occurrences in the main text, the word 'SNiPer' has been changed to 'Sniper'. Also, references to Figure 3b and Figure 3c have been reversed. The article has been corrected online. The authors and editors apologize for these errors.