Cold Spring Harbor Laboratory

About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.

Transitions in Distinct Histone H3 Methylation Patterns at the Heterochromatin Domain Boundaries

Abstract: Eukaryotic genomes are organized into discrete structural and functional chromatin domains. Here, we show that distinct site-specific histone H3 methylation patterns define euchromatic and heterochromatic chromosomal domains within a 47-kilobase region of the mating-type locus in fission yeast. H3 methylated at lysine 9 (H3 Lys9), and its interacting Swi6 protein, are strictly localized to a 20-kilobase silent heterochromatic interval. In contrast, H3 methylated at lysine 4 (H3 Lys4) is specific to the surrounding euchromatic regions. Two inverted repeats flanking the silent interval serve as boundary elements to mark the borders between heterochromatin and euchromatin. Deletions of these boundary elements lead to spreading of H3 Lys9 methylation and Swi6 into neighboring sequences. Furthermore, the H3 Lys9 methylation and corresponding heterochromatin-associated complexes prevent H3 Lys4 methylation in the silent domain.

GAGE: A critical evaluation of genome assemblies and assembly algorithms

Abstract: New sequencing technology has dramatically altered the landscape of whole-genome sequencing, allowing scientists to initiate numerous projects to decode the genomes of previously unsequenced organisms. The lowest-cost technology can generate deep coverage of most species, including mammals, in just a few days. The sequence data generated by one of these projects consist of millions or billions of short DNA sequences (reads) that range from 50 to 150 nt in length. These sequences must then be assembled de novo before most genome analyses can begin. Unfortunately, genome assembly remains a very difficult problem, made more difficult by shorter reads and unreliable long-range linking information. In this study, we evaluated several of the leading de novo assembly algorithms on four different short-read data sets, all generated by Illumina sequencers. Our results describe the relative performance of the different assemblers as well as other significant differences in assembly difficulty that appear to be inherent in the genomes themselves. Three overarching conclusions are apparent: first, that data quality, rather than the assembler itself, has a dramatic effect on the quality of an assembled genome; second, that the degree of contiguity of an assembly varies enormously among different assemblers and different genomes; and third, that the correctness of an assembly also varies widely and is not well correlated with statistics on contiguity. To enable others to replicate our results, all of our data and methods are freely available, as are all assemblers used in this study.

The Selaginella genome identifies genetic changes associated with the evolution of vascular plants.

Abstract: Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.

Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization

Abstract: A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation.

Fragile X-related protein and VIG associate with the RNA interference machinery

Abstract: RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.