oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 5 )

2018 ( 10 )

2017 ( 13 )

2016 ( 9 )

Custom range...

Search Results: 1 - 10 of 5642 matches for " Renato Paro "
All listed articles are free for downloading (OA Articles)
Page 1 /5642
Display every page Item
RNA at the steering wheel
Sabine Schmitt, Renato Paro
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-5-218
Abstract: The large majority of DNA sequences of most eukaryotic genomes do not possess any coding capacity. Nevertheless, many of these sequences are transcribed, generating a vast amount of noncoding RNA [1,2]. We are still far from fully understanding the role of this seemingly nonproductive large-scale transcription. In some situations, however, the process of intergenic transcription and the noncoding RNAs generated have been linked to the epigenetic control of gene expression. Intergenic transcripts appear to influence the way chromatin - the complex of DNA and the histones that package it - controls gene expression [3].A prominent example of this type of epigenetic gene regulation is the mechanism of cellular memory, well studied in the fruit fly Drosophila melanogaster. Cellular memory is the inheritance of a cell's gene-expression program through cell division, and this memory is a prerequisite for the maintenance of cell fates throughout development. In Drosophila, cis-regulatory DNA element called PRE/TREs consisting of Polycomb group response elements and Trithorax group response elements are central components of the mechanism for establishing cellular memory. Poly-comb group (PcG) and Trithorax group (TrxG) proteins are targeted to these elements, promoting the formation of repressive (via PcG) or transcriptionally competent (via TrxG) chromatin structures [4]. In tissues where a PRE/TRE-controlled gene is active, transcription through the PRE and TRE sequences can be observed [5,6]. This suggests that the transcription acts as an anti-silencing mechanism, preventing the PcG proteins from repressing their target genes [7]. A recent study by Sanchez-Elsner et al. [8] now provides a first insight into the molecular basis of this anti-silencing mechanism. The authors show that the noncoding RNAs originating from a PRE/TRE stay associated with the element and anchor a histone-modifying enzyme, thus directly controlling the establishment of an epigenetically activate
Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
Federico Comoglio,Renato Paro
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003419
Abstract: In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable for origin function, suggesting that HMs may act combinatorially in analogy to the histone code hypothesis for transcriptional regulation. In contrast to gene expression however, the relationship between combinations of chromatin features and DNA replication timing has not yet been demonstrated. Here, by exploiting a comprehensive data collection consisting of 95 CBPs and HMs we investigated their combinatorial potential for the prediction of DNA replication timing in Drosophila using quantitative statistical models. We found that while combinations of CBPs exhibit moderate predictive power for replication timing, pairwise interactions between HMs lead to accurate predictions genome-wide that can be locally further improved by CBPs. Independent feature importance and model analyses led us to derive a simplified, biologically interpretable model of the relationship between chromatin landscape and replication timing reaching 80% of the full model accuracy using six model terms. Finally, we show that pairwise combinations of HMs are able to predict differential DNA replication timing across different cell types. All in all, our work provides support to the existence of combinatorial HM patterns for DNA replication and reveal cell-type independent key elements thereof, whose experimental investigation might contribute to elucidate the regulatory mode of this fundamental cellular process.
Evolutionary Plasticity of Polycomb/Trithorax Response Elements in Drosophila Species
Arne Hauenschild,Leonie Ringrose,Christina Altmutter,Renato Paro,Marc Rehmsmeier
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0060261
Abstract: cis-Regulatory DNA elements contain multiple binding sites for activators and repressors of transcription. Among these elements are enhancers, which establish gene expression states, and Polycomb/Trithorax response elements (PREs), which take over from enhancers and maintain transcription states of several hundred developmentally important genes. PREs are essential to the correct identities of both stem cells and differentiated cells. Evolutionary differences in cis-regulatory elements are a rich source of phenotypic diversity, and functional binding sites within regulatory elements turn over rapidly in evolution. However, more radical evolutionary changes that go beyond motif turnover have been difficult to assess. We used a combination of genome-wide bioinformatic prediction and experimental validation at specific loci, to evaluate PRE evolution across four Drosophila species. Our results show that PRE evolution is extraordinarily dynamic. First, we show that the numbers of PREs differ dramatically between species. Second, we demonstrate that functional binding sites within PREs at conserved positions turn over rapidly in evolution, as has been observed for enhancer elements. Finally, although it is theoretically possible that new elements can arise out of nonfunctional sequence, evidence that they do so is lacking. We show here that functional PREs are found at nonorthologous sites in conserved gene loci. By demonstrating that PRE evolution is not limited to the adaptation of preexisting elements, these findings document a novel dimension of cis-regulatory evolution.
A Deterministic Analysis of Genome Integrity during Neoplastic Growth in Drosophila
Cem Sievers, Federico Comoglio, Makiko Seimiya, Gunter Merdes, Renato Paro
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087090
Abstract: The development of cancer has been associated with the gradual acquisition of genetic alterations leading to a progressive increase in malignancy. In various cancer types this process is enabled and accelerated by genome instability. While genome sequencing-based analysis of tumor genomes becomes increasingly a standard procedure in human cancer research, the potential necessity of genome instability for tumorigenesis in Drosophila melanogaster has, to our knowledge, never been determined at DNA sequence level. Therefore, we induced formation of tumors by depletion of the Drosophila tumor suppressor Polyhomeotic and subjected them to genome sequencing. To achieve a highly resolved delineation of the genome structure we developed the Deterministic Structural Variation Detection (DSVD) algorithm, which identifies structural variations (SVs) with high accuracy and at single base resolution. The employment of long overlapping paired-end reads enables DSVD to perform a deterministic, i.e. fragment size distribution independent, identification of a large size spectrum of SVs. Application of DSVD and other algorithms to our sequencing data reveals substantial genetic variation with respect to the reference genome reflecting temporal separation of the reference and laboratory strains. The majority of SVs, constituted by small insertions/deletions, is potentially caused by erroneous replication or transposition of mobile elements. Nevertheless, the tumor did not depict a loss of genome integrity compared to the control. Altogether, our results demonstrate that genome stability is not affected inevitably during sustained tumor growth in Drosophila implying that tumorigenesis, in this model organism, can occur irrespective of genome instability and the accumulation of specific genetic alterations.
Evolutionary Plasticity of Polycomb/Trithorax Response Elements in Drosophila Species
Arne Hauenschild equal contributor,Leonie Ringrose equal contributor ,Christina Altmutter,Renato Paro,Marc Rehmsmeier
PLOS Biology , 2008, DOI: 10.1371/journal.pbio.0060261
Abstract: cis-Regulatory DNA elements contain multiple binding sites for activators and repressors of transcription. Among these elements are enhancers, which establish gene expression states, and Polycomb/Trithorax response elements (PREs), which take over from enhancers and maintain transcription states of several hundred developmentally important genes. PREs are essential to the correct identities of both stem cells and differentiated cells. Evolutionary differences in cis-regulatory elements are a rich source of phenotypic diversity, and functional binding sites within regulatory elements turn over rapidly in evolution. However, more radical evolutionary changes that go beyond motif turnover have been difficult to assess. We used a combination of genome-wide bioinformatic prediction and experimental validation at specific loci, to evaluate PRE evolution across four Drosophila species. Our results show that PRE evolution is extraordinarily dynamic. First, we show that the numbers of PREs differ dramatically between species. Second, we demonstrate that functional binding sites within PREs at conserved positions turn over rapidly in evolution, as has been observed for enhancer elements. Finally, although it is theoretically possible that new elements can arise out of nonfunctional sequence, evidence that they do so is lacking. We show here that functional PREs are found at nonorthologous sites in conserved gene loci. By demonstrating that PRE evolution is not limited to the adaptation of preexisting elements, these findings document a novel dimension of cis-regulatory evolution.
PcG-Mediated Higher-Order Chromatin Structures Modulate Replication Programs at the Drosophila BX-C
Federica Lo Sardo equal contributor,Chiara Lanzuolo equal contributor,Federico Comoglio,Marco De Bardi,Renato Paro,Valerio Orlando
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003283
Abstract: Polycomb group proteins (PcG) exert conserved epigenetic functions that convey maintenance of repressed transcriptional states, via post-translational histone modifications and high order structure formation. During S-phase, in order to preserve cell identity, in addition to DNA information, PcG-chromatin-mediated epigenetic signatures need to be duplicated requiring a tight coordination between PcG proteins and replication programs. However, the interconnection between replication timing control and PcG functions remains unknown. Using Drosophila embryonic cell lines, we find that, while presence of specific PcG complexes and underlying transcription state are not the sole determinants of cellular replication timing, PcG-mediated higher-order structures appear to dictate the timing of replication and maintenance of the silenced state. Using published datasets we show that PRC1, PRC2, and PhoRC complexes differently correlate with replication timing of their targets. In the fully repressed BX-C, loss of function experiments revealed a synergistic role for PcG proteins in the maintenance of replication programs through the mediation of higher-order structures. Accordingly, replication timing analysis performed on two Drosophila cell lines differing for BX-C gene expression states, PcG distribution, and chromatin domain conformation revealed a cell-type-specific replication program that mirrors lineage-specific BX-C higher-order structures. Our work suggests that PcG complexes, by regulating higher-order chromatin structure at their target sites, contribute to the definition and the maintenance of genomic structural domains where genes showing the same epigenetic state replicate at the same time.
Distinct Roles of Hand2 in Initiating Polarity and Posterior Shh Expression during the Onset of Mouse Limb Bud Development
Antonella Galli ,Dimitri Robay,Marco Osterwalder,Xiaozhong Bao,Jean-Denis Bénazet,Muhammad Tariq,Renato Paro,Susan Mackem,Rolf Zeller
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000901
Abstract: The polarization of nascent embryonic fields and the endowment of cells with organizer properties are key to initiation of vertebrate organogenesis. One such event is antero-posterior (AP) polarization of early limb buds and activation of morphogenetic Sonic Hedgehog (SHH) signaling in the posterior mesenchyme, which in turn promotes outgrowth and specifies the pentadactylous autopod. Inactivation of the Hand2 transcriptional regulator from the onset of mouse forelimb bud development disrupts establishment of posterior identity and Shh expression, which results in a skeletal phenotype identical to Shh deficient limb buds. In wild-type limb buds, Hand2 is part of the protein complexes containing Hoxd13, another essential regulator of Shh activation in limb buds. Chromatin immunoprecipitation shows that Hand2-containing chromatin complexes are bound to the far upstream cis-regulatory region (ZRS), which is specifically required for Shh expression in the limb bud. Cell-biochemical studies indicate that Hand2 and Hoxd13 can efficiently transactivate gene expression via the ZRS, while the Gli3 repressor isoform interferes with this positive transcriptional regulation. Indeed, analysis of mouse forelimb buds lacking both Hand2 and Gli3 reveals the complete absence of antero-posterior (AP) polarity along the entire proximo-distal axis and extreme digit polydactyly without AP identities. Our study uncovers essential components of the transcriptional machinery and key interactions that set-up limb bud asymmetry upstream of establishing the SHH signaling limb bud organizer.
Autonomia do educando na escola fundamental: um tema negligenciado
Paro, Vitor Henrique;
Educar em Revista , 2011, DOI: 10.1590/S0104-40602011000300013
Abstract: this article deals with the autonomy (in the pedagogical process and in daily school practice) as a student's right and an indispensable requirement for high quality education. it is part of a broad study about the structure of the school and it is based on a qualitative research done at a public school in s?o paulo city. to the theoretical contribution from the educational science, this essay adds an analysis of data about interviews with educators and observations of daily pedagogical practice and activities carried out at school. the implications of both political and educational autonomy of the student are emphasized, in order to conclude in favor of the importance of this issue and warn about its paradoxical neglect by the public educational policies.
Forma??o de gestores escolares: a atualidade de José Querino Ribeiro
Paro, Vitor Henrique;
Educa??o & Sociedade , 2009, DOI: 10.1590/S0101-73302009000200008
Abstract: the celebration of josé querino ribeiro's birthday centennial led this paper to rescue the relevant points in the work of this very important author of studies on school administration in brazil. its stresses the supposed paradox herein present and highlights two alternatives to train school administrators: one, specific and "technical", is grounded in the methods and principles of capitalist companies, with "managerial" appeal and strong emphasis on how to control someone else's work while the other is based on pedagogical foundations and the potential of education as a democratic practice.
Implica??es do caráter político da educa??o para a administra??o da escola pública
Paro, Vitor Henrique;
Educa??o e Pesquisa , 2002, DOI: 10.1590/S1517-97022002000200002
Abstract: starting from a broad conception of politics - transcending the mere struggle for power, and identifying politics with a human-social practice that has the purpose of making possible the living together of groups and people - the article elaborates an equally broad concept of democracy that, not being restricted to its parliamentary or electoral meaning, is understood as a social practice that builds the free and peaceful coexistence of individuals and groups that assert themselves as historical agents. taken then as a historical-cultural actualization through which takes place the construction of the historical man through the acquisition of culture, education has its political dimension highlighted precisely because of this ability to endow the human being with their historical and plural condition, due to which they necessarily have to live with other individuals and groups. by analyzing the dialogic and reinforcing character of the subjectivity of the educated, through which the authentic education must take place in order to be coherent with its function of builder of the historical man, the work seeks to bring forward the nature of the education process not just as political practice but also as an intrinsically democratic practice. within this framework the article considers the implications of this political and democratic condition to the quality of teaching, to the school management practice, and to the studies in school management.
Page 1 /5642
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.