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Mediterranean coasts are prone to tsunamis due to high seismicity in some well-known areas near plate margins. However, tsunamis have a low frequency of occurrence despite having highly destructive potential. The low frequency of occurrence and historicity of the most destructive events lead to minimizing or neglecting this risk. Past research identified socio-demographic and spatial factors that may affect tsunami risk perception. This research is based on CATI survey (Computer Assisted Telephone Interview) to a sample of 5842 respondents designed to investigate whether and how risk perception and risk knowledge were affected by a major event such as the 1908 Reggio Calabria Messina tsunami, by making a comparison between areas hit by that event and unaffected areas, also providing some explanatory hypotheses. Despite differences between Calabria and Sicily, data show higher levels of tsunami risk perception in the area affected by the 1908 event, along with a major role of interpersonal sources, playing a relevant role in information gathering and understanding. Research also suggests the need to better integrate different sources of knowledge to improve people’s understanding so as to effectively cope with tsunami risk.

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.

X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element ( Xce ). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncRNA , one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist . This effect is counteracted by enhanced binding of Rex1 in DxPas34 , another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34 , and that Lppnx represents a decisive factor in explaining the action of the Xce .

Supplementary data: The following is the Supplementary data to this article: Acrobat PDF file (2MB) available at: https://ars.els-cdn.com/content/image/1-s2.0-S2212420921007329-mmc1.pdf Copyright © 2022 The Authors. 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. COST (European Cooperation in Science and Technology); Royal Society, UK (grant number CHL\R1\180173); Severo Ochoa Centers of Excellence Program (CEX 2018-000797-S) funded by MCIN/ AEI /10.13039/501100011033; Lloyd's Tercentenary Research Foundation, the Lighthill Risk Network, and the Lloyd's Register Foundation-Data Centric Engineering Programme of the Alan Turing Institute.

Genomic repeats have been intensely studied as regulatory elements controlling gene transcription, splicing and genome architecture. Our understanding of the role of the repetitive RNA such as the RNA coming from genomic repeats, or repetitive sequences embedded in mRNA/lncRNAs, in nuclear and cellular functions is instead still limited. In this review we discuss evidence supporting the multifaceted roles of repetitive RNA and RNA binding proteins in nuclear organization, gene regulation, and in the formation of dynamic membrane-less aggregates. We hope that our review will further stimulate research in the consolidating field of repetitive RNA biology.

Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer's disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson's disease, autism spectrum condition, attention-deficit hyperactivity disorder, Tourette's syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment.

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.

Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist, an X-linked long non-coding RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated and spreads along the future inactive X chromosome. Contextually, it recruits repressive histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is tightly coupled to differentiation and its expression is under the control of both pluripotency and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist regulation in differentiating ES cells, linked to its control and prevention of spurious transcription factor interactions occurring within Xist regulatory regions. Our findings have a broader relevance, in the context of complex, developmentally-regulated gene expression., Communications Biology, 4 (1), ISSN:2399-3642

Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR., Communications Biology, 4 (1), ISSN:2399-3642

The tsunami risk perception survey is promoted by the Tsunami Alert Centre of the National Institute of Geophysics and Volcanology, operating within the Italian System for Tsunami Alert (SiAM) with the Civil Protection Department and ISPRA, and acting as Tsunami Service Provider in the NEAMTWS.Conducting studies on tsunami risk perception is important in order to obtain data on population’s knowledge and awareness, and understanding people’s perception of tsunami risk. These data are going to be added to those from two previous surveys on tsunami risk perception being issued in 2018 and 2020, to integrate the available knowledge on these issues and will provide publics, experts and policy makers with relevant tools to implement risk mitigation policies. The third phase of the survey was completed in January 2021, administering a total of 4,207 questionnaires to the population living on the coastal areas of Sicily, Campania, Latium and Sardinia, in addition to the 1,635 interviewees considered in previous surveys.The survey used a semi-structured questionnaire consisting of 27 items, with closed alternative questions, and four sets of Likert scale questions. The questionnaire was optimized for CATI administration, taking into account the need for conciseness and comprehensibility of the questions.All the studied regions are located in the central Mediterranean basin (including central and southern Tyrrhenian Sea, Sardinian Sea, Sicily Channel), some of which are characterized by high tsunami hazard, and in some cases they have been affected by recorded tsunamis in a close or distant past. Some regions are located in areas where potential seismic tsunami sources are present, others surround waters where active volcanoes exist, both on islands (such as Stromboli, Vulcano) and below the sea (Marsili, Palinuro). In addition, the four studied regions have a high risk exposure due to the high density of population living on, or visiting the coastal areas for tourism. In the areas where the questionnaire was administered, five highly populated regional capitals are located, including Palermo, Messina, Naples, Rome and Cagliari, together with other important towns (such as Catania, Siracusa, Trapani, Salerno, Olbia etc.). Moreover, the coastal shores involved in the survey, live of a significant tourist affluence in the summer period (and not only), with many tourist facilities and large hotels located along the coasts.The survey's main aim is to analyze the perception of tsunami risk by the coastal population and to correlate levels of tsunami risk perception with scientific data from probabilistic tsunami hazard assessment (PTHA) for the considered coastal area. We will present some preliminary results of this last survey, with a comparison with the previous analyses on other regions in southern Italy.

The onset of random X inactivation in mouse requires the switch from a symmetric to an asymmetric state, where the identities of the future inactive and active X chromosomes are assigned. Here we show that RIF1 and KAP1 are two fundamental factors for the definition of the asymmetry. Our data show that at the onset of mESC differentiation, upregulation of the long non-coding RNA Tsix weakens the symmetric RIF1 association with the Xist promoter, and opens a window of opportunity for a more stable association of KAP1. KAP1 is required to sustain high levels of Tsix, thus reinforcing and propagating the asymmetry, and, as a result, marking the future active X chromosome. Furthermore, we show that RIF1 association with the future inactive X chromosome is essential for Xist upregulation. This double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1, thus coordinates the identification of the inactive and active X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.

We present the results of an ongoing research for assessing tsunami risk perception in southern Italy. The study is motivated by the need of addressing a sound communication strategy for tsunami risk reduction, related to the activities of the Tsunami Alert Centre (CAT) of INGV, operating within the framework of the Italian civil protection system. The area of the second step of this study includes five regions of Italy (Basilicata, Calabria, Molise, Puglia, Sicily), facing on Adriatic, Ionian and Tyrrhenian seas, located in one of the most hazardous areas of the Mediterranean. In all the area the memory of relevant tsunamis is loose, since the last destructive event dates back to 1908 (due to the Messina-Reggio Calabria M~7 earthquake). The main goal of this study is to verify how people’s perception of tsunami risk compares with the hazard assessed by scientific data, and which are the main factors controlling people’s knowledge and awareness. We analysed a sample of more than 1,600 interviewees representing about 4 million people living in the coastal municipalities of the five considered regions. Results show that risk perception appears to be generally low, with significant differences among different areas, likely due to the the time elapsed since the last events. The survey results for the first two investigated regions (Calabria and Puglia, see Cerase et al., NHESS, 2019) showed that people’s perception and understanding of tsunamis are affected by media accounts of the mega-tsunamis of Sumatra 2004 and Japan 2011. At the same time, the risk posed by small tsunamis is basically underrated or neglected, posing some critical questions for risk mitigation strategies, particularly in touristic areas. Furthermore, the survey’s results show that for lay people the word ‘tsunami’ has a different meaning with respect to the Italian traditional word ‘maremoto’, implying that the same physical phenomenon would be understood in two different ways by younger, educated people and elders with low education level. In addition, people have high expectations from authorities, CPAs, research institutions about warnings. Moreover, living in different coastal areas appears to have a significant influence on the way tsunami hazard is perceived: Interviewees of Tyrrhenian Calabria are more likely to associate tsunami risk to volcanoes with respect to those living in the Ionian coastal areas, coherently with the presence of Aeolian volcanic islands and feared submarine volcanoes in the Tyrrhenian. A somehow unexpected result is that TV emerges as the most relevant source of knowledge for 90% of the sample. Some categories declared to prefer getting early warnings through broadcast media and sirens rather than receiving by SMS or apps, suggesting the need for redundancy and modulation of EW messages. We will present an update of the survey which is presently ongoing, related to the five regions. These results could help in addressing risk communication and mitigation policies.

Background Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. While MeCP2 mutations are lethal in most males, females survive birth but show severe neurological defects. Because X-chromosome inactivation (XCI) is a random process, approximately 50% of the cells silence the wild-type (WT) copy of the MeCP2 gene. Thus, reactivating the silent WT copy of MeCP2 could provide therapeutic intervention for RTT. Methods Toward this goal, we screened ~ 28,000 small-molecule compounds from several libraries using a MeCP2-luciferase reporter cell line and cortical neurons from a MeCP2-EGFP mouse model. We used gain/increase of luminescence or fluorescence as a readout of MeCP2 reactivation and tested the efficacy of these drugs under different drug regimens, conditions, and cellular contexts. Results We identified inhibitors of the JAK/STAT pathway as XCI-reactivating agents, both by in vitro and ex vivo assays. In particular, we show that AG-490, a Janus Kinase 2 (JAK2) kinase inhibitor, and Jaki, a pan JAK/STAT inhibitor, are capable of reactivating MeCP2 from the inactive X chromosome, in different cellular contexts. Conclusions Our results suggest that inhibition of the JAK/STAT pathway is a new potential pathway to reinstate MeCP2 gene expression as an efficient RTT treatment.

Polycomb steps to inactivate X XX females silence one of their X chromosomes. This involves a process whereby a noncoding RNA known as Xist coats one of the X chromosomes and recruits chromatin silencing factors. The Polycomb complexes PRC1 and PRC2 are also known to be involved in X chromosome inactivation. Almeida et al. elucidate a key role of a specific complex, PCGF3/5-PRC1, in initiating Polycomb recruitment by Xist RNA. They further demonstrate that Polycomb recruitment is critical for Xist-mediated chromosome silencing and female embryogenesis. Science , this issue p. 1081

Mice carrying single chromosome substitutions (consomic mice) provide a unique platform for investigating complex phenotypes. A proportion of such phenotypes fall into the category of transgressive phenotypes, i.e. heritable extreme phenotypes lying outside the range of either parent. We hypothesized that analysis of transgressive phenotype in consomic mice potentially reveals unique cellular and molecular signatures associated with extreme phenotypic variations. We used a system-biology approach to build a reference set of 571 transgressive phenotypes in consomic mice using phenome metadata and additional 13 B-cell specific transgressive phenotypes using experimental data. As a proof of concept, we investigated clinically-relevant hyper-IgM phenotype. A combination of flow-cytometry, RNA-Sequencing and in-vitro validation confirmed that the hyper-IgM is associated with defective B-cell lymphopoiesis at the cellular and the down-regulation of the CCR7 gene at the molecular level. Our approach provides a complete pipeline to discover and validate transgressive phenotypes relevant to health and disease conditions.

Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders.

The rise of racism in Europe In recent years online racism has seen a quick and serious growth in many European and non-European countries, till to become a worrying global phenomenon. One of the most striking examples of such process is the rise of White Supremacist Movements online. Their strategy mainly consists in disguising their hidden political agenda and attempting to subvert and destroy civil rights by presenting their standpoints through an overturn of the rhetoric of the civil rights movement. Undoubtedly, the increasing racism which is rotten in hidden racist expressions, is exploiting “favorable” conditions as the financial crisis, the increase of social conflicts and the rise of populist issues in politics. In Italy, as an example, UNAR, the Italian national anti-discrimination Office, documented that complaints for online racism weighed for 30.9% of the overall cases involving the media (UNAR, 2013). Similar situations also occurred in other European countries such as Slovenia, Finland, Hungary and United Kingdom, as it emerged by part of the research carried out within the framework of the European project LIGHT ON. Nowadays, racist claims are often hidden under a subtle and sophisticated rethoric. In fact, a huge amount of disguised racist contents is currently published on the Internet in form of occasional bigotry or individuals’ outburst, whereas they are, as a matter of fact, intended to foster racist attitudes among people and to support the “normalization” of racism. Some scholars defined as “common sense racism” or “rational racism” talking against immigrants, refugees, minority members (as well as homosexuals and disabled) as undesirable and avoiding to be labeled as “racist”.

Xist long non-coding RNA induces heterochromatinization of the X-chromosome by accumulating in large ribonucleoprotein assemblies. We suggest that Xist regulates X chromosome inactivation by recruiting RNA-binding proteins via a mechanism of liquid-liquid phase separation. To support this hypothesis, we provide evidence that Xist forms ribonucleoprotein condensates that are similiar in size, shape and protein composition to paraspeackles and stress granules. We show that Xist interactome is particularly enriched in proteins that are intrinsically disordered and capable of phase separating. We suggest that Xist reinforces Xi heterochromatinization by sequestering repressive complexes, such as Polycomb proteins, in an indirect way through phase separation. This process is complementary to the canonical chromatin-mediated recruitment.

The word media hype is often used as rhetorical argument to dismiss waves of media attention as overblown, disproportional and exaggerated. But these explosive news waves, as well as - nowadays - the twitter storms, are object of scientific research, because they are an important phenomenon in the public area. Sometimes it is indeed 'much ado about nothing' but in many cases these media storms have play an important role in political issues, scandals and crises. Twitter storms sometimes ruin reputations within hours. Although different concepts are used, such as media hypes, news waves, media storms, information cascades or risk amplification, all the studies in this book refer to the same process in which key events trigger a chain of reactions and interactions, building up huge news waves in the media or rapidly spreading social epidemics in the social media. This book offers the first comprehensive overview of this important topic. It is not only interesting for scholars and students in media and journalism, but also for professionals in PR and communication, crisis communication and reputation management.

Recent experimental evidence indicates that lncRNAs can act as regulatory molecules in the context of development and disease. Xist, the master regulator of X chromosome inactivation, is a classic example of how lncRNAs can exert multi-layered and fine-tuned regulatory functions, by acting as a molecular scaffold for recruitment of distinct protein factors. In this review, we discuss the methodologies employed to define Xist RNA structures and the tight interplay between structural clues and functionality of lncRNAs. This model of modular function dictated by structure, can be also generalized to other lncRNAs, beyond the field of X chromosome inactivation, to explain common features of similarly folded RNAs.

Long noncoding RNAs (lncRNAs, which comprise 68% of the human transcriptome with average length of 1,000 nt) interact with various RNA-binding proteins (RBPs) to mediate cellular functions1. Identification of lncRNA interactions through experimental methods is challenging and can be complemented by the use of computational models to predict protein partners. Yet it is currently impractical to calculate RBP–lncRNA interactions for large transcripts2.We introduce Global Score as a means to predict protein interactions with large RNAs (http://service.tartaglialab.com/new_submission/globalscore).

Summary The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element. Deletion of XR-PID abolishes Xist-dependent Polycomb recruitment, in turn abrogating Xist-mediated gene silencing and reversing Xist-induced chromatin inaccessibility. We identify the RNA-binding protein hnRNPK as the principal XR-PID binding factor required to recruit PCGF3/5-PRC1. Accordingly, synthetically tethering hnRNPK to Xist RNA lacking XR-PID is sufficient for Xist-dependent Polycomb recruitment. Our findings define a key pathway for Polycomb recruitment by Xist RNA, providing important insights into mechanisms of chromatin modification by non-coding RNA., Graphical Abstract, Highlights • A 600 nt element in Xist RNA, XR-PID, is required for Polycomb recruitment • Deletion of XR-PID abrogates Xist-mediated chromosome silencing • hnRNPK binds XR-PID to recruit the Polycomb-initiating complex PCGF3/5-PRC1 • Tethering hnRNPK to Xist RNA bypasses the requirement for XR-PID, This study advances our understanding of the molecular mechanism of X chromosome inactivation in mammals, defining XR-PID, the critical element in Xist RNA that recruits Polycomb complexes to the inactive X chromosome, and further demonstrating that the RNA binding protein hnRNPK bridges XR-PID with the initiating Polycomb complex, PCGF3/5-PRC1.

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.