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Malhotra V.,Center for Genomic Regulation
Cold Spring Harbor perspectives in biology | Year: 2011

The serine/threonine protein kinase D (PKD) is recruited to the trans-Golgi network (TGN) by binding diacylglycerol (DAG) and the ARF1 GTPase. PKD, at the TGN, promotes the production of phosphatidylinositol-4 phosphate (PI4P) by activating the lipid kinase phophatidylinositol 4-kinase III (PI4KIII). PI4P recruits proteins such as oxysterol-binding protein 1 (OSBP) and ceramide transport protein (CERT) that control sphingolipid and sterol levels at the TGN. CERT mediated transport of ceramide to the TGN, we suggest, is used for increasing the local production and concentration of DAG. Once the crucial concentration of DAG is achieved, OSBP and CERT dissociate from the TGN on phosphorylation by PKD and DAG is sequentially converted into phosphatidic acid (PA) and lyso-PA (LPA). Therefore, the net effect of the activated PKD at the TGN is the sequential production of the modified lipids DAG, PA, and LPA that are necessary for membrane fission to generate cell surface specific transport carriers. Source


Innan H.,Graduate University for Advanced Studies | Innan H.,Japan Science and Technology Agency | Kondrashov F.,Center for Genomic Regulation
Nature Reviews Genetics | Year: 2010

Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications. © 2010 Macmillan Publishers Limited. All rights reserved. Source


Dekker J.,University of Massachusetts Medical School | Marti-Renom M.A.,Genome Biology Group | Marti-Renom M.A.,Center for Genomic Regulation | Mirny L.A.,Massachusetts Institute of Technology
Nature Reviews Genetics | Year: 2013

How DNA is organized in three dimensions inside the cell nucleus and how this affects the ways in which cells access, read and interpret genetic information are among the longest standing questions in cell biology. Using newly developed molecular, genomic and computational approaches based on the chromosome conformation capture technology (such as 3C, 4C, 5C and Hi-C), the spatial organization of genomes is being explored at unprecedented resolution. Interpreting the increasingly large chromatin interaction data sets is now posing novel challenges. Here we describe several types of statistical and computational approaches that have recently been developed to analyse chromatin interaction data. © 2013 Macmillan Publishers Limited. Source


Tartaglia G.G.,Center for Genomic Regulation
BMC genomics | Year: 2014

BACKGROUND: The large amount of data produced by high-throughput sequencing poses new computational challenges. In the last decade, several tools have been developed for the identification of transcription and splicing factor binding sites.RESULTS: Here, we introduce the SeAMotE (Sequence Analysis of Motifs Enrichment) algorithm for discovery of regulatory regions in nucleic acid sequences. SeAMotE provides (i) a robust analysis of high-throughput sequence sets, (ii) a motif search based on pattern occurrences and (iii) an easy-to-use web-server interface. We applied our method to recently published data including 351 chromatin immunoprecipitation (ChIP) and 13 crosslinking immunoprecipitation (CLIP) experiments and compared our results with those of other well-established motif discovery tools. SeAMotE shows an average accuracy of 80% in finding discriminative motifs and outperforms other methods available in literature.CONCLUSIONS: SeAMotE is a fast, accurate and flexible algorithm for the identification of sequence patterns involved in protein-DNA and protein-RNA recognition. The server can be freely accessed at http://s.tartaglialab.com/new_submission/seamote. Source


Gabaldon T.,Center for Genomic Regulation
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

Peroxisomes are organelles bounded by a single membrane that can be found in all major groups of eukaryotes. A single evolutionary origin of this cellular compartment is supported by the presence, in diverse organisms, of a common set of proteins implicated in peroxisome biogenesis and maintenance. Their enzymatic content, however, can vary substantially across species, indicating a high level of evolutionary plasticity. Proteomic analyses have greatly expanded our knowledge on peroxisomes in some model organisms, including plants, mammals and yeasts. However, we still have a limited knowledge about the distribution and functionalities of peroxisomes in the vast majority of groups of microbial eukaryotes. Here, I review recent advances in our understanding of peroxisome diversity and evolution, with a special emphasis on peroxisomes in microbial eukaryotes. © 2010 The Royal Society. Source

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