X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells

X chromosome inactivation (XCI) is the dosage compensation mechanism that evolved in female mammals to correct the genetic imbalance of X-linked genes between sexes. X chromosome inactivation occurs in early development when one of the two X chromosomes of females is nearly-completely silenced. Differentiating Embryonic Stem cells (ESC) are regarded as a useful tool to study XCI, since they recapitulate many events occurring during early development. In this review we aim to summarise the advances in the field and to discuss the close connection between cell differentiation and X chromosome inactivation, with a particular focus on mouse ESCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-015-9597-5) contains supplementary material, which is available to authorized users

Tsunami risk perception in central and southern Italy

The Tsunami Alert Centre of the National Institute of Geophysics and Volcanology (CAT-INGV) has been promoting, since 2018, the study of tsunami risk perception in Italy. Between 2018 and 2021 a semi-structured questionnaire on the perception of tsunami risk was administered to a sample of 5842 citizens residing in 450 Italian coastal municipalities, representative of more than 12 million people. The survey was conducted with the computer-assisted telephone interviewing (CATI) methodology, described in Cerase et al. (2019), who published the results of the first pilot survey (about 1000 interviews). The large sample and the socio-demographic stratification give an excellent representation of the resident population in the surveyed Italian coastal municipalities. Moreover, in 2021 an optimized version of the questionnaire was also administered via Telepanel (a tool for collecting proportional and representative opinions of citizens) that was representative of the Italian population and included 1500 people distributed throughout the country. In this work we present the main results of the three survey phases, with a comparison among the eight surveyed regions and between the coastal regions and some coastal metropolitan cities involved in the investigations (Rome, Naples, Bari, Reggio Calabria, and Catania). Data analysis reveals heterogeneous and generally low tsunami risk perception. Some seaside populations, in fact, show a good perception of tsunami risk, while others, such as in Apulia and Molise, reveal a lower perception, most likely due to the long time elapsed since the last event and lack of memory. We do not find relevant differences related to the socio-demographic characteristics (age, gender) of the sample, whereas the education degree appears to affect people's perception. The survey shows that the respondents' predominant source of information on tsunamis is the television and other media sources (such as newspapers, books, films, internet), while the official sources (e.g., civil protection, local authorities, universities and research institutes) do not contribute significantly. Also, we find an interesting difference in people's understanding of the words tsunami and maremoto, the local term commonly used in Italy until the 2004 Sumatra–Andaman event, which should be taken into account in scientific and risk communication. The Telepanel survey, based on a nationwide sample, highlights a lower level of tsunami risk perception in comparison to average risk perception levels found in the coastal-municipality sample. Our results are being used to drive our communication strategy aimed at reducing tsunami risk in Italy, to activate dissemination and educational programs (data driven), to fill the data gap on tsunami risk perception in the North-Eastern Atlantic, Mediterranean and connected seas (NEAM) area, and to implement multilevel civil protection actions (national and local, top-down and bottom-up). Not least, outputs can address a better development of the UNESCO Tsunami Ready program in Italy.</p

Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription

Phase separation drives X-chromosome inactivation: a hypothesis

The long non-coding RNA Xist induces heterochromatinization of the X chromosome by recruiting repressive protein complexes to chromatin. Here we gather evidence, from the literature and from computational analyses, showing that Xist assemblies are similar in size, shape and composition to phase-separated condensates, such as paraspeckles and stress granules. Given the progressive sequestration of Xist’s binding partners during X-chromosome inactivation, we formulate the hypothesis that Xist uses phase separation to perform its function

Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription

Tsunami risk communication and management: Contemporary gaps and challenges

Very large tsunamis are associated with low probabilities of occurrence. In many parts of the world, these events have usually occurred in a distant time in the past. As a result, there is low risk perception and a lack of collective memories, making tsunami risk communication both challenging and complex. Furthermore, immense challenges lie ahead as population and risk exposure continue to increase in coastal areas. Through the last decades, tsunamis have caught coastal populations off-guard, providing evidence of lack of preparedness. Recent tsunamis, such as the Indian Ocean Tsunami in 2004, 2011 Tohoku and 2018 Palu, have shaped the way tsunami risk is perceived and acted upon. Based on lessons learned from a selection of past tsunami events, this paper aims to review the existing body of knowledge and the current challenges in tsunami risk communication, and to identify the gaps in the tsunami risk management methodologies. The important lessons provided by the past events call for strengthening community resilience and improvement in risk-informed actions and policy measures. This paper shows that research efforts related to tsunami risk communication remain fragmented. The analysis of tsunami risk together with a thorough understanding of risk communication gaps and challenges is indispensable towards developing and deploying comprehensive disaster risk reduction measures. Moving from a broad and interdisciplinary perspective, the paper suggests that probabilistic hazard and risk assessments could potentially contribute towards better science communication and improved planning and implementation of risk mitigation measures

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

Background: A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). Results: We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an `autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. Conclusions: 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi