Cell-cycle regulated transcription associates with DNA replication timing in yeast and human

Eukaryotic DNA replication follows a specific temporal program, with some genomic regions consistently replicating earlier than others, yet what determines this program is largely unknown. Highly transcribed regions have been observed to replicate in early S-phase in all plant and animal species studied to date, but this relationship is thought to be absent from both budding yeast and fission yeast. No association between cell-cycle regulated transcription and replication timing has been reported for any species. Here I show that in budding yeast, fission yeast, and human, the genes most highly transcribed during S-phase replicate early, whereas those repressed in S-phase replicate late. Transcription during other cell-cycle phases shows either the opposite correlation with replication timing, or no relation. The relationship is strongest near late-firing origins of replication, which is not consistent with a previously proposed model -- that replication timing may affect transcription -- and instead suggests a potential mechanism involving the recruitment of limiting replication initiation factors during S-phase. These results suggest that S-phase transcription may be an important determinant of DNA replication timing across eukaryotes, which may explain the well-established association between transcription and replication timing

Using protein complexes to predict phenotypic effects of gene mutation

The best predictor of a protein's knockout phenotype is shown to be the knockout phenotype of other proteins that are present in a protein complex with it

Evolutionary rate depends on number of protein-protein interactions independently of gene expression level

BACKGROUND: Whether or not a protein's number of physical interactions with other proteins plays a role in determining its rate of evolution has been a contentious issue. A recent analysis suggested that the observed correlation between number of interactions and evolutionary rate may be due to experimental biases in high-throughput protein interaction data sets. DISCUSSION: The number of interactions per protein, as measured by some protein interaction data sets, shows no correlation with evolutionary rate. Other data sets, however, do reveal a relationship. Furthermore, even when experimental biases of these data sets are taken into account, a real correlation between number of interactions and evolutionary rate appears to exist. SUMMARY: A strong and significant correlation between a protein's number of interactions and evolutionary rate is apparent for interaction data from some studies. The extremely low agreement between different protein interaction data sets indicates that interaction data are still of low coverage and/or quality. These limitations may explain why some data sets reveal no correlation with evolutionary rates

Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date; after six months, it is available under a Creative Commons License.-- et al.The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture.M.I., M.S.A., S.W.R., and H.B.F. were funded by NIH grant 1R21HG005240-01A1. H.B.F. is an Alfred P. Sloan Fellow and Pew Scholar in the Biomedical Sciences. J.J.T., A.F-M., O.B., E.C-M., and J.L.G-S. were funded by grants BFU2010-14839, CSD2007-00008, and Proyecto de Excelencia CVI-3488.Peer reviewe

YARSI UNIVERSITY PROGRAM TO MEET THE DEMAND OF STUDENT’S ENGLISH FLUENCY WITH TOEIC AS THE ASSESSMENT TOOL

Abstract: A test is only a measurement tool of a learning process. The important part is the learning process itself; how the process can help learners acquire English as a foreign language that enables them to compete in the working environment. To measure the process, TOEIC with all its parts was meant to measure learners’ ability to communicate in English. Teachers should not be focusing on the test but more on the approaches that allow the students to have adequate and sophisticated listening, reading, and writing skills to exchange information and to negotiate meaning in real life. Many university level English teachers are trapped within the rules that students should achieve a 550 or 605 TOEIC score to graduate. Instead of helping the students to acquire the language as a communication tool, they tend to focus more on getting the students to master the test. This is what teachers should deal with, not only facilitate students to learn the language but at the same time help them to do the test well. Despite the challenge of facing students who lack motivation and have very basic English skills, Yarsi University Language Lab is setting up several programs and approaches that allow students to acquire the language and enable them to communicate in the target language which is eventually measured by an instrument called TOEIC. Keywords: Language Acquisition, direct and indirect test, discrete and intregativ

The Quantitative Genetics of Phenotypic Robustness

Phenotypic robustness, or canalization, has been extensively investigated both experimentally and theoretically. However, it remains unknown to what extent robustness varies between individuals, and whether factors buffering environmental variation also buffer genetic variation. Here we introduce a quantitative genetic approach to these issues, and apply this approach to data from three species. In mice, we find suggestive evidence that for hundreds of gene expression traits, robustness is polymorphic and can be genetically mapped to discrete genomic loci. Moreover, we find that the polymorphisms buffering genetic variation are distinct from those buffering environmental variation. In fact, these two classes have quite distinct mechanistic bases: environmental buffers of gene expression are predominantly sex-specific and trans-acting, whereas genetic buffers are not sex-specific and often cis-acting. Data from studies of morphological and life-history traits in plants and yeast support the distinction between polymorphisms buffering genetic and environmental variation, and further suggest that loci buffering different types of environmental variation do overlap with one another. These preliminary results suggest that naturally occurring polymorphisms affecting phenotypic robustness could be abundant, and that these polymorphisms may generally buffer either genetic or environmental variation, but not both