1,721,034 research outputs found
Local chromatin context regulates the genetic requirements of the heterochromatin spreading reaction
No full textHeterochromatin spreading, the expansion of repressive chromatin structure from sequence-specific nucleation sites, is critical for stable gene silencing. Spreading re-establishes gene-poor constitutive heterochromatin across cell cycles but can also invade gene-rich euchromatin de novo to steer cell fate decisions. How chromatin context (i.e. euchromatic, heterochromatic) or different nucleation pathways influence heterochromatin spreading remains poorly understood. Previously, we developed a single-cell sensor in fission yeast that can separately record heterochromatic gene silencing at nucleation sequences and distal sites. Here we couple our quantitative assay to a genetic screen to identify genes encoding nuclear factors linked to the regulation of heterochromatin nucleation and the distal spreading of gene silencing. We find that mechanisms underlying gene silencing distal to a nucleation site differ by chromatin context. For example, Clr6 histone deacetylase complexes containing the Fkh2 transcription factor are specifically required for heterochromatin spreading at constitutive sites. Fkh2 recruits Clr6 to nucleation-distal chromatin sites in such contexts. In addition, we find that a number of chromatin remodeling complexes antagonize nucleation-distal gene silencing. Our results separate the regulation of heterochromatic gene silencing at nucleation versus distal sites and show that it is controlled by context-dependent mechanisms. The results of our genetic analysis constitute a broad community resource that will support further analysis of the mechanisms underlying the spread of epigenetic silencing along chromatin
Perinuclear chromatin anchoring in Caenorhabditis elegans embryos : CEC-4 characterization and function
Full text linkThis thesis consists of four chapters.
Chapter 1 is an introduction based in reviews from the Gasser lab, to which I have contributed. The main message of each review is kept but they are arranged or modified in a way to avoid redundancy and provide clarity. Additional relevant literature that is not discussed adequately in either of the reviews has been included. The chapter gives an updated overview of the field of spatial organization of chromatin in the interphase nucleus.
Chapter 2 presents the work published in Cell, 2015. It is an experimental chapter in which I present the identification, characterization and function of a novel C. elegans chromodomain protein called CEC-4 (Caenorhabditis elegans chromodomain protein 4), which mediates the anchoring of chromatin at the nuclear periphery in C. elegans embryos. Experiments were primarily performed by myself, but I indicate where others have carried our experimental work for this publication.
Chapter 3 presents unpublished data that further characterizes CEC-4.
Finally, Chapter 4 places the work presented in the thesis in the context of spatial chromatin organization and provides a future outlook based on this study
Dams in the nucleus: The dynamics of heterochromatin positioning at nuclear structures in the mammalian nucleus
No full textGenome organization and gene regulation are important contributors to cell identity and normal behavior, but remain poorly understood. In this PhD thesis, I have studied how the genome is organized around nuclear substructures, such as the nuclear lamina and nucleoli, and what the functional role is of this organization. To do this, I have developed a new experimental methodology to profile where these structures interact with the genome, and used this to test the dynamics during the cell cycle and after various perturbation experiments. Overall, I have identified several factors that modulate nuclear positioning of the genome, and correlated nuclear positioning at the substructures with various functional consequences
A Cas9 TRIP through chromatin: CRI!PR-Cas9 editing and DNA repair in the context of chromatin
No full textStudies on the DNA double strand break repair pathway balance in the context of chromati
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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