Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development

Acquisition of cell fate is thought to rely on the specific interaction of remote cis-regulatory modules (CRMs), for example, enhancers and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly within multicellular developing organisms. In the present study, we employ Hi-M, a single-cell spatial genomics approach, to detect CRM–promoter looping interactions within topologically associating domains (TADs) during early Drosophila development. By comparing cis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses reveal that multiple CRMs spatially coalesce to form hubs. Loops and CRM hubs are established early during development, before the emergence of TADs. Moreover, CRM hubs are formed, in part, via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach provides insight into the role of CRM–promoter interactions in defining transcriptional states, as well as distinct cell types.Fil: Espínola, Sergio Martín. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Université de Montpellier. Centre de Biologie Structurale; FranciaFil: Götz, Markus. Université de Montpellier. Centre de Biologie Structurale; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Bellec, Maelle. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Messina, Olivier. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Fiche, Jean Bernard. Université de Montpellier. Centre de Biologie Structurale; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Houbron, Christophe. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Centre National de la Recherche Scientifique; FranciaFil: Dejean, Matthieu. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; FranciaFil: Reim, Ingolf. Universitat Erlangen Nuremberg; AlemaniaFil: Cardozo Gizzi, Andres Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; ArgentinaFil: Lagha, Mounia. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; FranciaFil: Nollmann, Marcelo. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Université de Montpellier. Centre de Biologie Structurale; Franci

The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development

A single nucleotide polymorphism causing constitutive activation of Vav1 results in increased natural Treg generation and is responsible for the imbalance between Vav1 GEF and adaptor functions

A Spontaneous Mutation of the Rat Themis Gene Leads to Impaired Function of Regulatory T Cells Linked to Inflammatory Bowel Disease

Spontaneous or chemically induced germline mutations, which lead to Mendelian phenotypes, are powerful tools to discover new genes and their functions. Here, we report an autosomal recessive mutation that occurred spontaneously in a Brown-Norway (BN) rat colony and was identified as causing marked T cell lymphopenia. This mutation was stabilized in a new rat strain, named BNm for “BN mutated.” In BNm rats, we found that the T cell lymphopenia originated in the thymus, was intrinsic to CD4 T lymphocytes, and was associated with the development of an inflammatory bowel disease. Furthermore, we demonstrate that the suppressive activity of both peripheral and thymic CD4+ CD25bright regulatory T cells (Treg) is defective in BNm rats. Complementation of mutant animals with BN Treg decreases disease incidence and severity, thus suggesting that the impaired Treg function is involved in the development of inflammatory bowel disease in BNm rats. Moreover, the cytokine profile of effector CD4 T cells is skewed toward Th2 and Th17 phenotypes in BNm rats. Linkage analysis and genetic dissection of the CD4 T cell lymphopenia in rats issued from BNm×DA crosses allowed the localization of the mutation on chromosome 1, within a 1.5 megabase interval. Gene expression and sequencing studies identified a frameshift mutation caused by a four-nucleotide insertion in the Themis gene, leading to its disruption. This result is the first to link Themis to the suppressive function of Treg and to suggest that, in Themis-deficient animals, defect of this function is involved in intestinal inflammation. Thus, this study highlights the importance of Themis as a new target gene that could participate in the pathogenesis of immune diseases characterized by chronic inflammation resulting from a defect in the Treg compartment

Comparing Notes: Recording and Criticism

This chapter charts the ways in which recording has changed the nature of music criticism. It both provides an overview of the history of recording and music criticism, from the advent of Edison’s Phonograph to the present day, and examines the issues arising from this new technology and the consequent transformation of critical thought and practice

Wider Still and Wider: British Music Criticism since the Second World War

This chapter provides the first historical examination of music criticism in Britain since the Second World War. In the process, it also challenges the simplistic prevailing view of this being a period of decline from a golden age in music criticism

Translating Corporate Social Responsibility

National audienc

Recherche sur le rôle des maîtres de stage dans la formation des enseignants: Proposition d’un dispositif de formation

http://www.agers.cfwb.be/prof/dossiers/recheduc/rech1.asp?page=5info:eu-repo/semantics/publishe