The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes

Ueber das Daempfungs- und Ermuedungsverhalten einiger Faserverbundwerkstoffe

The present study investigates the influence of fatigue load on the stress-strain behavior of balanced angular laminates. The nonlinear behavior is described by an elastic-viscoplastic material model. The model parameters are determined, and the model behavior is used to draw conclusions to the micromechanical supporting behavior of the materials under investigation. A loading and measurement system was developed to carry out the experiments. This system exposes fiber composite specimens to loads with a preselectable deformation profile and analyses the stress-strain curves of the specimens under investigation. By appropriately selecting the electrical and mechanical components, and using a computer program for control, measurement and analysis, adapted to the same, it is possible to make a very exact determination of the time relation of strain and stress, which is of significance to this study. Owing to the almost identical setup of the measurement facilities for stress and strain, errors in the measurement of the phase position of both parameters were minimized. In specified load cycle number intervals during fatigue loading, the rheologic behavior of the specimens under investigation was registered under load via four strain amplitudes and three-and-a-half frequency decades. (orig.)Available from TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman