Center for Genomic Regulation
Center for Genomic Regulation
Flames N.,Howard Hughes Medical Institute |
Flames N.,Center for Genomic Regulation |
Flames N.,Institute Biomedicina Of Valencia Ibv Csic |
Hobert O.,Howard Hughes Medical Institute
Annual Review of Neuroscience | Year: 2011
Monoaminergic neurons are critical functional components of all nervous systems across phylogeny. The terminally differentiated state of individual types of monoaminergic neurons is defined by the coordinated expression of a battery of genes that instructs the synthesis and transport of specific monoamines, such as serotonin or dopamine. Dysfunction or deregulation of several of these enzymes and transporter system has been proposed to be the underlying basis of several pathological conditions. We review here the state of knowledge of the nature of the transcriptional regulatory programs that control the expression of what we term monoaminergic gene batteries (enzymes and transporters for specific monoamines) and thereby define the terminally differentiated state of monoaminergic neurons. We review several case studies in vertebrate and invertebrate model systems and propose that the coordinated expression of the genes that define individual monoaminergic cell types may be brought about by transcriptional coregulatory strategies. © 2011 by Annual Reviews. All rights reserved.
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.
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.
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.
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.
Solanas G.,Center for Genomic Regulation |
Benitah S.A.,Center for Genomic Regulation |
Benitah S.A.,University Pompeu Fabra |
Benitah S.A.,Catalan Institution for Research and Advanced Studies
Nature Reviews Molecular Cell Biology | Year: 2013
In the past years, our view of the molecular and cellular mechanisms that ensure the self-renewal of the skin has dramatically changed. Several populations of stem cells have been identified that differ in their spatio-temporal contribution to their compartment in steady-state and damaged conditions, suggesting that epidermal stem cell heterogeneity is far greater than previously anticipated. There is also increasing evidence that these different stem cells require a tightly controlled spatial and temporal communication between other skin residents to carry out their function. © 2013 Macmillan Publishers Limited. All rights reserved.
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.
Gekas C.,Center for Genomic Regulation
Blood | Year: 2013
The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (αIIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity on serial transplantations and showed a marked myeloid bias compared with CD41- HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout (KO) mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO-associated defects are long-term transplantable, HSC-derived and, in part, mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as transforming growth factor β1. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age and highlights the dogma of HSC regulation by their progeny.
Igea A.,Center for Genomic Regulation |
Mendez R.,Center for Genomic Regulation
EMBO Journal | Year: 2010
Meiotic progression is driven by the sequential translational activation of maternal messenger RNAs stored in the cytoplasm. This activation is mainly induced by the cytoplasmic elongation of their poly(A) tails, which is mediated by the cytoplasmic polyadenylation element (CPE) present in their 3′ untranslated regions. Although polyadenylation in prophase I and metaphase I is mediated by the CPE-binding protein 1 (CPEB1), this protein is degraded during the first meiotic division. Thus, raising the question of how the cytoplasmic polyadenylation required for the second meiotic division is achieved. In this work, we show that CPEB1 generates a positive loop by activating the translation of CPEB4 mRNA, which, in turn, replaces CPEB1 and drives the transition from metaphase I to metaphase II. We further show that CPEB1 and CPEB4 are differentially regulated by phase-specific kinases, generating the need of two sequential CPEB activities to sustain cytoplasmic polyadenylation during all the meiotic phases. Altogether, this work defines a new element in the translational circuit that support an autonomous transition between the two meiotic divisions in the absence of DNA replication. © 2010 European Molecular Biology Organization | All Rights Reserved.
Gekas C.,Center for Genomic Regulation |
Graf T.,Catalan Institution for Research and Advanced Studies
Journal of Experimental Medicine | Year: 2010
The era of induced pluripotent stem (iPS) cells carries with it the promise of virtually unlimited sources of autologous cells for regenerative medicine. However, efficiently differentiating iPS cells into fully functional mature cell types remains challenging. A new study reporting the formation of fully functional platelets from human iPS (hiPS) cells improves upon recent efforts to generate this enucleated cell type, which remains in high demand for therapeutic transfusions. Notably, their lack of nucleus renders platelets unable to retain the pluripotent or tumorigenic properties of iPS cells. © 2010 Gekas and Graf.