scholarly journals Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Peter Chovanec ◽  
Amanda J. Collier ◽  
Christel Krueger ◽  
Csilla Várnai ◽  
Claudia I. Semprich ◽  
...  

AbstractThe transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and develop a network-graph approach to examine the atlas at multiple spatial scales. We uncover highly connected promoter hubs that change substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merge to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identify widespread state-specific differences in enhancer activity and interactivity that correspond with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide multilayered insights into the chromatin-based gene regulatory control of human pluripotent states.

2019 ◽  
Author(s):  
Peter Chovanec ◽  
Amanda J. Collier ◽  
Christel Krueger ◽  
Csilla Várnai ◽  
Stefan Schoenfelder ◽  
...  

SUMMARYA complex and poorly understood interplay between 3D genome organisation, transcription factors and chromatin state underpins cell identity. To gain a systems-level understanding of this interplay, we generated a high-resolution atlas of annotated chromatin interactions in naïve and primed human pluripotent stem cells and developed a network-graph approach to examine the atlas at multiple spatial scales. Investigating chromatin interactions as a network uncovered highly connected hubs that changed substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merged to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. Importantly, we identified state-specific differences in enhancer activity and interactivity that corresponded with widespread reconfiguration of transcription factor binding and target gene expression. These findings provide multilayered insights into the gene regulatory control of human pluripotency and our systems-based network approach could be applied broadly to uncover new principles of 3D genome organisation.


2019 ◽  
Vol 19 (2) ◽  
pp. 92-100 ◽  
Author(s):  
Charlotte Moretti ◽  
Isabelle Stévant ◽  
Yad Ghavi-Helm

Abstract Ever since Thomas Hunt Morgan’s discovery of the chromosomal basis of inheritance by using Drosophila melanogaster as a model organism, the fruit fly has remained an essential model system in studies of genome biology, including chromatin organisation. Very much as in vertebrates, in Drosophila, the genome is organised in territories, compartments and topologically associating domains (TADs). However, these domains might be formed through a slightly different mechanism than in vertebrates due to the presence of a large and potentially redundant set of insulator proteins and the minor role of dCTCF in TAD boundary formation. Here, we review the different levels of chromatin organisation in Drosophila and discuss mechanisms and factors that might be involved in TAD formation. The dynamics of TADs and enhancer–promoter interactions in the context of transcription are covered in the light of currently conflicting results. Finally, we illustrate the value of polymer modelling approaches to infer the principles governing the three-dimensional organisation of the Drosophila genome.


2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.


1996 ◽  
Vol 34 (1) ◽  
pp. 27
Author(s):  
Sue Yon Shim ◽  
Ki Joon Sung ◽  
Young Ju Kim ◽  
In Soo Hong ◽  
Myung Soon Kim ◽  
...  

2016 ◽  
Vol 2 (2) ◽  
pp. 40
Author(s):  
Miriam Aparicio

This study tests some hypotheses included in the psycho-social-communicational paradigm, which emphasizes the cognitive effects of the media and the role of the psychosocial subject as the recipient


2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.


GEOgraphia ◽  
2018 ◽  
Vol 19 (41) ◽  
pp. 39
Author(s):  
Agripino Souza Coelho Neto

Resumo: O presente texto pretende analisar o papel das ações coletivas (associações, cooperativas e sindicatos de agricultores) no acionamento e na ativação das escalas geográficas para o desenvolvimento de suas atividades. O estudo foi realizado no Espaço Sisaleiro da Bahia (Brasil), onde um conjunto significativo de associações e cooperativas de agricultores e sindicatos de trabalhadores rurais tem se organizado em torno das escalas espaciais para viabilizar sua ação político-institucional e econômico-produtiva. A ação desses coletivos organizados em rede tem permitido a conformação e o fortalecimento de novas escalas de ação política, como no caso da criação do conselho territorial para viabilização da implantação de políticas de governo. Cooperativas, associações e sindicatos se apoiam nas escalas para compor organizações em diferentes níveis escalares (escala local, escala regional, escala do estado federado e escala nacional), buscando fortalecer seus propósitos e ampliar seu poder de barganha e influência. Analisando o comportamento espacial dessas variadas modalidades de ações coletivas, é possível considerar que elas desenvolvem políticas de escala, ou seja, a escala passa a significar muito mais que uma categoria de análise, mas se torna uma categoria da prática social e política. Nesse sentido, parte-se do pressuposto de que os grupos humanos produzem e tornam efetivas suas próprias escalas visando a alcançar suas metas e organizar seus comportamentos coletivos. Palavras-chave: Escala. Rede. Cooperativismo. Associativismo. Sindicalismo. Espaço Sisaleiro da Bahia. SCALE POLICIES AND THE DEVELOPMENT OF NETWORK STRATEGIES OF COLLECTIVE ACTIONS IN THE SISAL REGION OF BAHIA (BRAZIL)Abstract: This paper aims to analyze the role of collective initiatives of associations, cooperatives and farmers’ unions in the mobilization and activation of geographical scales for the development of their activities. The study was conducted in the Sisal Region of Bahia (Brazil), where a significant number of farmers associations and cooperatives and rural workers’ unions have been organizing their actions around spatial scales to enable their political-institutional and economic-productive influence. The gathering and action of these organized groups in a network have allowed the establishment and strengthening of new scales of political action, as seem in the case of the creation of a territorial council to facilitate the implementation of government policies. Cooperatives, associations, and unions rely on scales to form organizations at different scale levels (local, regional, federal and national scales), seeking to strengthen their performance and increase their bargaining power and influence. After analyzing the spatial behavior of these various forms of collective actions, it’s reasonable to say that they develop scale policies, which means the scale becomes more than a category of analysis, but also a category of social and political practice. In this sense, it’s assumed that human groups produce and utilize the scales in order to reach their goals and organize their own collective behaviors. Keywords: Scale. Network. Cooperativism. Associativism. Syndicalism. Sisal Region of Bahia. POLITIQUES D’ÉCHELLE ET FORMATION DES STRATÉGIES-RÉSEAU DES ACTIONS COLLECTIVES DANS LA RÉGION DU SISAL DE L’ÉTAT DE BAHIA Resumé: Cet article analyse le rôle des actions collectives (associations, coopératives et syndicats d’agriculteurs) dans la prise en compte et l’utilisation des échelles géographiques pour le développement de leurs activités. L’étude a été menée dans la région du sisal à Bahia (Brésil), où un ensemble important d’associations et de coopératives d’agriculteurs et de syndicats de travailleurs ruraux se sont organisés autour d’échelles spatiales pour que puisse être mise en place leur action politique et institutionnelle, économique et productive. L’action de ces groupements organisés en réseaux a permis la conformation et le renforcement de nouvelles échelles d’action politique, comme lors de la création du conseil territorial, pour permettre la mise en œuvre des politiques gouvernementales. Les coopératives, les associations et les syndicats prennent les échelles comme point de départ pour former des organisations à différents niveaux scalaires (échelle locale, échelle régionale, échelle fédérée et échelle nationale), dans le but de renforcer leurs objectifs et d’accroître leur pouvoir de négociation et d’influence. Si nous analysons le comportement spatial de ces diverses formes d’action collective il est possible de considérer qu’ils développent des politiques d’échelle, à savoir l’échelle vient signifier bien plus qu’une catégorie d’analyse, puisqu’elle devient une catégorie de la pratique sociale et politique. En ce sens, on suppose que les groupes humains produisent et rendent efficaces leurs propres échelles pour atteindre leurs objectifs et organiser leurs comportements collectifs. Mots-clés: Échelle. Réseau. Coopérativisme. Associations. Syndicalisme. Région du sisal de l’État de Bahia.


2020 ◽  
Vol 13 (12) ◽  
pp. e239286
Author(s):  
Kumar Nilesh ◽  
Prashant Punde ◽  
Nitin Shivajirao Patil ◽  
Amol Gautam

Ossifying fibroma (OF) is a rare, benign, fibro-osseous lesion of the jawbone characterised by replacement of the normal bone with fibrous tissue. The fibrous tissue shows varying amount of calcified structures resembling bone and/or cementum. The central variant of OF is rare, and shows predilection for mandible among the jawbone. Although it is classified as fibro-osseous lesion, it clinically behaves as a benign tumour and can grow to large size, causing bony swelling and facial asymmetry. This paper reports a case of large central OF of mandible in a 40-year-old male patient. The lesion was treated by segmental resection of mandible. Reconstruction of the surgical defect was done using avascular fibula bone graft. Role of three-dimensional printing of jaw and its benefits in surgical planning and reconstruction are also highlighted.


2021 ◽  
Vol 2021 (5) ◽  
Author(s):  
Adrien Fiorucci ◽  
Romain Ruzziconi

Abstract The gravitational charge algebra of generic asymptotically locally (A)dS spacetimes is derived in n dimensions. The analysis is performed in the Starobinsky/Fefferman-Graham gauge, without assuming any further boundary condition than the minimal falloffs for conformal compactification. In particular, the boundary structure is allowed to fluctuate and plays the role of source yielding some symplectic flux at the boundary. Using the holographic renormalization procedure, the divergences are removed from the symplectic structure, which leads to finite expressions. The charges associated with boundary diffeomorphisms are generically non-vanishing, non-integrable and not conserved, while those associated with boundary Weyl rescalings are non-vanishing only in odd dimensions due to the presence of Weyl anomalies in the dual theory. The charge algebra exhibits a field-dependent 2-cocycle in odd dimensions. When the general framework is restricted to three-dimensional asymptotically AdS spacetimes with Dirichlet boundary conditions, the 2-cocycle reduces to the Brown-Henneaux central extension. The analysis is also specified to leaky boundary conditions in asymptotically locally (A)dS spacetimes that lead to the Λ-BMS asymptotic symmetry group. In the flat limit, the latter contracts into the BMS group in n dimensions.


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