http://genomebiology.com/ The latest research articles published by Genome Biology 2010-03-17T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Evolutionary divergent organisms often share developmental anatomies despite vast differences between their genome sequences. The social amoebae Dictyostelium discoideum and Dictyostelium purpureum have similar developmental morphologies although their genomes are as divergent as those of man and jawed fish. Results: Here we show that the anatomical similarities are accompanied by extensive transcriptome conservation. Using RNA sequencing we compared the abundance and developmental regulation of all the transcripts in the two species. In both species, most genes are developmentally regulated and the greatest expression changes occur during the transition from unicellularity to multicellularity. The developmental regulation of transcription is highly conserved between orthologs in the two species. In addition to timing of expression, the level of mRNA production is also conserved between orthologs and is consistent with the intuitive notion that transcript abundance correlates with the amount of protein required. Furthermore, the conservation of transcriptomes extends to cell-type specific expression. Conclusions: These findings suggest that developmental programs are remarkably conserved at the transcriptome level, considering the great evolutionary distance between the genomes. Moreover, this transcriptional conservation may be responsible for the similar developmental anatomies of Dictyostelium discoideum and Dictyostelium purpureum. http://genomebiology.com/2010/11/3/R35 Anup Parikh Edward Roshan Miranda Mariko Katoh-Kurasawa Danny Fuller Gregor Rot Lan Zagar Tomaz Curk Richard Sucgang Rui Chen Blaz Zupan William Loomis Adam Kuspa Gad Shaulsky Genome Biology 2010, 11:R35 2010-03-17T00:00:00Z doi:10.1186/gb-2010-11-3-r35 Genome Biology 1465-6906 11 R35 2010-03-17T00:00:00Z PDF We have developed a new strategy for de novo prediction of splice junctions in short read RNA-seq data, suitable for detection of novel splicing events and chimeric transcripts. When tested on mouse RNA-seq data, over 31,000 splice events were predicted, of which 88% bridged between two regions separated by at most 100 kb, and 74% connected two exons of the same RefSeq gene. Our method also reports genomic rearrangements such as insertions and deletions. http://genomebiology.com/2010/11/3/R34 Adam Ameur Anna Wetterbom Lars Feuk Ulf Gyllensten Genome Biology 2010, 11:R34 2010-03-17T00:00:00Z doi:10.1186/gb-2010-11-3-r34 Genome Biology 1465-6906 11 R34 2010-03-17T00:00:00Z PDF The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote. http://genomebiology.com/2010/11/3/110 Genome Biology 2010, 11:110 2010-03-16T00:00:00Z doi:10.1186/gb-2010-11-3-110 Genome Biology 1465-6906 11 110 2010-03-16T00:00:00Z XML The heat-shock protein 90 (Hsp90) is currently thought to buffer eukaryotic cells against perturbations caused by pre-existing cryptic genetic variation. A new study suggests that the buffering function of Hsp90 could instead be due to its repression of de novo transposon-mediated mutagenesis. http://genomebiology.com/2010/11/3/109 Genome Biology 2010, 11:109 2010-03-16T00:00:00Z doi:10.1186/gb-2010-11-3-109 Genome Biology 1465-6906 11 109 2010-03-16T00:00:00Z XML Background: The general transcription factor TFIIB and its antagonist negative cofactor 2 (NC2) are hallmarks of RNA polymerase II (RNAPII) transcription. Both factors bind TATA box-binding protein at promoters in a mutually exclusive manner. Dissociation of NC2 is thought to be followed by TFIIB association and subsequent preinitiation complex formation. TFIIB dissociates upon RNAPII promoter clearance, thereby providing a specific measure for steady-state preinitiation complex levels. As yet, genome-scale promoter mapping of human TFIIB has not been reported. It thus remains elusive how human core promoters contribute to preinitiation complex formation in vivo. Results: We compare target genes of TFIIB and NC2 in human B cells and analyze associated core promoter architectures. TFIIB occupancy is positively correlated with gene expression, with the vast majority of promoters being GC-rich and lacking defined core promoter elements. TATA elements but not the previously in vitro defined TFIIB recognition elements are enriched in some 4-5% of the genes. NC2 binds to a highly related target gene set. Nonetheless, subpopulations show strong variations in factor ratios: whereas high TFIIB/NC2 ratios select for promoters with focused start sites and conserved core elements, high NC2/TFIIB ratios correlate to multiple start-site promoters lacking defined core elements. Conclusions: TFIIB and NC2 are global players that occupy active genes. Preinitiation complex formation is independent of core elements at the majority of genes. TATA and TATA-like elements dictate TFIIB occupancy at a subset of genes. Biochemical data support a model in which preinitiation complex but not TBP-NC2 complex formation is regulated. http://genomebiology.com/2010/11/3/R33 Thomas Albert Korbinian Grote Stefan Boeing Michael Meisterernst Genome Biology 2010, 11:R33 2010-03-15T00:00:00Z doi:10.1186/gb-2010-11-3-r33 Genome Biology 1465-6906 11 R33 2010-03-15T00:00:00Z PDF We introduce Pathicular (http://bioinformatics.psb.ugent.be/software/details/Pathicular), a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks. Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data. A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance. http://genomebiology.com/2010/11/3/R32 Anagha Joshi Thomas Van Parys Yves Van de Peer Tom Michoel Genome Biology 2010, 11:R32 2010-03-15T00:00:00Z doi:10.1186/gb-2010-11-3-r32 Genome Biology 1465-6906 11 R32 2010-03-15T00:00:00Z PDF The discovery of several new structured non-coding RNAs in bacterial and archaeal genomes and metagenomes raises burning questions about their biological and biochemical functions.See related research article by Weinberg et al.: http://genomebiology.com/2010/11/3/R31 http://genomebiology.com/2010/11/3/108 Genome Biology 2010, 11:108 2010-03-15T00:00:00Z doi:10.1186/gb-2010-11-3-108 Genome Biology 1465-6906 11 108 2010-03-15T00:00:00Z XML Background: Structured noncoding RNAs perform many functions that are essential for protein synthesis, RNA processing, and gene regulation. Structured RNAs can be detected by comparative genomics, in which homologous sequences are identified and inspected for mutations that conserve RNA secondary structure. Results: By applying a comparative genomics-based approach to genome and metagenome sequences from bacteria and archaea, we identified 104 candidate structured RNAs and inferred putative functions for many of these. Twelve candidate metabolite-binding RNAs were identified, three of which were validated, including one reported herein that binds the coenzyme S-adenosylmethionine. Newly identified cis-regulatory RNAs are implicated in photosynthesis or nitrogen regulation in cyanobacteria, purine and one-carbon metabolism, stomach infection by Helicobacter, and many other physiological processes. A candidate riboswitch termed crcB is represented in both bacteria and archaea. Another RNA motif may control gene expression from 3' untranslated regions of mRNAs, which is unusual for bacteria. Many noncoding RNAs that likely act in trans are also revealed and several of the noncoding RNA candidates are found mostly or exclusively in metagenome DNA sequences. Conclusions: This work greatly expands the variety of highly-structured noncoding RNAs known to exist in bacteria and archaea and provides a starting point for biochemical and genetic studies needed to validate their biological functions. Given the sustained rate of RNA discovery over several similar projects, we expect that far more structured RNAs remain to be discovered from bacterial and archaeal organisms.See associated research highlight by Westhof: http://genomebiology.com/2010/11/3/108 http://genomebiology.com/2010/11/3/R31 Zasha Weinberg Joy Wang Jarrod Bogue Jingying Yang Keith Corbino Ryan Moy Ronald Breaker Genome Biology 2010, 11:R31 2010-03-15T00:00:00Z doi:10.1186/gb-2010-11-3-r31 Genome Biology 1465-6906 11 R31 2010-03-15T00:00:00Z PDF We systematically analyzed the relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast. Co-fitness predicted gene functions distinct from those derived from other assays and identified conditionally-sensitive protein complexes. Co-inhibitory compounds were weakly correlated by structure and therapeutic class. We developed an algorithm predicting protein targets of chemical compounds and verified its accuracy with experimental testing. Fitness data provide a novel, systems-level perspective on the cell. http://genomebiology.com/2010/11/3/R30 Maureen Hillenmeyer Elke Ericson Ronald Davis Corey Nislow Daphne Koller Guri Giaever Genome Biology 2010, 11:R30 2010-03-12T00:00:00Z doi:10.1186/gb-2010-11-3-r30 Genome Biology 1465-6906 11 R30 2010-03-12T00:00:00Z PDF Background: Approximately 35% of human genes contain introns within the 5' untranslated region (UTR). Introns in 5'UTRs differ from those in coding regions and 3'UTRs with respect to nucleotide composition, length distribution and density. Despite their presumed impact on gene regulation, the evolution and possible functions of 5'UTR introns remain largely unexplored. Results: We performed a genome-scale computational analysis of 5'UTR introns in humans. We discovered that the most highly expressed genes tended to have short 5'UTR introns rather than having long 5'UTR introns or lacking 5'UTR introns entirely. Although we found no correlation in 5'UTR intron presence or length with variance in expression across tissues, which might have indicated a broad role in expression-regulation, we observed an uneven distribution of 5'UTR amongst genes in specific functional categories. In particular, genes with regulatory roles were surprisingly enriched in having 5'UTR introns. Finally, we analyzed the evolution of 5'UTR introns in non-receptor protein tyrosine kinases (NRTK), and identified a conserved DNA motif enriched within the 5'UTR introns of human NRTKs. Conclusions: Our results suggest that human 5'UTR introns enhance the expression of some genes in a length-dependent manner. While many 5'UTR introns are likely to be evolving neutrally, their relationship with gene expression and overrepresentation among regulatory genes, taken together, suggest that complex evolutionary forces are acting on this distinct class of introns. http://genomebiology.com/2010/11/3/R29 Can Cenik Adnan Derti Joseph Mellor Gabriel Berriz Frederick Roth Genome Biology 2010, 11:R29 2010-03-11T00:00:00Z doi:10.1186/gb-2010-11-3-r29 Genome Biology 1465-6906 11 R29 2010-03-11T00:00:00Z PDF