Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

ABSTRACTAccessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). Whereas stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of cis-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq datasets and used it to analyze nucleosome dynamics at stimulus-regulated cis-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing however different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.

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Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome.

10.1101/2021.10.21.465269 ◽

2021 ◽

Author(s):

Miguel Martinez-Ara ◽

Federico Comoglio ◽

Joris van Arensbergen ◽

Bas van Steensel

Keyword(s):

Mammalian Cells ◽

Mouse Genome ◽

Regulatory Elements ◽

Genomic Context ◽

Systematic Analysis ◽

Chromatin Folding ◽

Reporter Assays ◽

Mouse Cells ◽

Genomic Regions ◽

Single Promoter

Gene expression is in part controlled by cis-regulatory elements (CREs) such as enhancers and repressive elements. Anecdotal evidence has indicated that a CRE and a promoter need to be biochemically compatible for promoter regulation to occur, but this compatibility has remained poorly characterised in mammalian cells. We used high-throughput combinatorial reporter assays to test thousands of CRE - promoter pairs from three Mb-sized genomic regions in mouse cells. This revealed that CREs vary substantially in their promoter compatibility, ranging from striking specificity for a single promoter to quantitative differences in activation across a broad set of promoters. More than half of the tested CREs exhibit significant promoter selectivity. Housekeeping promoters tend to have similar CRE preferences, but other promoters exhibit a wide diversity of compatibilities. Higher-order TF motif combinations may account for compatibility. CRE-promoter selectivity does not correlate with looping interactions in the native genomic context, suggesting that chromatin folding and compatibility are two orthogonal mechanisms that confer specificity to gene regulation.

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Regulation and Impact of Chromatin Decondensation in Mammalian Cells

Blood ◽

10.1182/blood.v128.22.sci-51.sci-51 ◽

2016 ◽

Vol 128 (22) ◽

pp. SCI-51-SCI-51

Author(s):

Rafael Casellas

Keyword(s):

B Cells ◽

B Cell ◽

Histone Acetylation ◽

Single Molecule ◽

Mammalian Cells ◽

Cell Activation ◽

Conflicts Of Interest ◽

Regulatory Elements ◽

Nucleosome Remodeling ◽

Topological Features

Abstract 50 years ago Vincent Allfrey and colleagues discovered that lymphocyte activation promotes histone acetylation and gene expression. Recent studies clarified that G0 B cells proportionally amplify their transcriptome upon stimulation by a mechanism that involves Myc and TFIIH. We now show that B cell chromatin undergoes massive decondensation by the amplification of histone acetylation, methylation, and nucleosome remodeling. Super-resolution microscopy revealed that histone acetylation triggers rapid spreading of chromatin nanodomains from the periphery to the entire nucleus. Furthermore, nanodomains decompact into single nucleosome fibers by a process that requires Myc and ATP production. Using single molecule tracking, we show that chromatin decompaction increases the dynamics of transcription factor binding. Architecturally, B cell activation mediates a marked shift from long-range to short-range interactions and the formation of loops and contact domains that facilitate interaction between cognate regulatory elements. The data thus reveal the epigenetic and topological features that support transcriptome amplification, and help explain the primed nature of B cells. Disclosures No relevant conflicts of interest to declare.

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CONTEXT-INDEPENDENT FUNCTION OF A CHROMATIN BOUNDARY IN VIVO

10.1101/2021.02.11.430727 ◽

2021 ◽

Author(s):

Andréa Willemin ◽

Lucille Lopez-Delisle ◽

Christopher Chase Bolt ◽

Marie-Laure Gadolini ◽

Denis Duboule ◽

...

Keyword(s):

Boundary Element ◽

Gene Cluster ◽

Target Genes ◽

Regulatory Elements ◽

Nuclear Space ◽

Genomic Context ◽

Mouse Development ◽

Architectural Proteins ◽

Genomic Regions ◽

The Impact

ABSTRACTMammalian genomes are partitioned into sub-megabase to megabase-sized units of preferential interactions called topologically associating domains or TADs, which are likely important for the proper implementation of gene regulatory processes. These domains provide structural scaffolds for distant cis regulatory elements to interact with their target genes within the three-dimensional nuclear space and architectural proteins such as CTCF as well as the cohesin complex participate in the formation of the boundaries between them. However, the importance of the genomic context in providing a given DNA sequence the capacity to act as a boundary element remains to be fully investigated. To address this question, we randomly relocated a topological boundary functionally associated with the mouse HoxD gene cluster and show that it can indeed act similarly outside its initial genomic context. In particular, the relocated DNA segment recruited the required architectural proteins and induced a significant depletion of contacts between genomic regions located across the integration site. The host chromatin landscape was re-organized, with the splitting of the TAD wherein the boundary had integrated. These results provide evidence that topological boundaries can function independently of their site of origin, under physiological conditions during mouse development.AUTHOR SUMMARYDuring development, enhancer sequences tightly regulate the spatio-temporal expression of target genes often located hundreds of kilobases away. This complex process is made possible by the folding of chromatin into domains, which are separated from one another by specific genomic regions referred to as boundaries. In order to understand whether such boundary sequences require their particular genomic contexts to achieve their isolating effect, we analyzed the impact of introducing one such boundary, taken from the HoxD gene cluster, into a distinct topological domain. We show that this ectopic boundary splits the host domain into two sub-domains and affects the expression levels of a neighboring gene. We conclude that this sequence can work independently from its genomic context and thus carries all the information necessary to act as a boundary element.

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Quota Women Are Threatening to Men

Swiss Journal of Psychology ◽

10.1024/1421-0185/a000195 ◽

2017 ◽

Vol 76 (3) ◽

pp. 107-116 ◽

Cited By ~ 4

Author(s):

Klea Faniko ◽

Till Burckhardt ◽

Oriane Sarrasin ◽

Fabio Lorenzi-Cioldi ◽

Siri Øyslebø Sørensen ◽

...

Keyword(s):

Decision Making ◽

Organizational Performance ◽

Gender Stereotypes ◽

Perceived Threat ◽

Preferential Treatment ◽

Public Sector Employees ◽

Different Types ◽

Low Levels ◽

Women In Decision Making ◽

The Impact

Abstract. Two studies carried out among Albanian public-sector employees examined the impact of different types of affirmative action policies (AAPs) on (counter)stereotypical perceptions of women in decision-making positions. Study 1 (N = 178) revealed that participants – especially women – perceived women in decision-making positions as more masculine (i.e., agentic) than feminine (i.e., communal). Study 2 (N = 239) showed that different types of AA had different effects on the attribution of gender stereotypes to AAP beneficiaries: Women benefiting from a quota policy were perceived as being more communal than agentic, while those benefiting from weak preferential treatment were perceived as being more agentic than communal. Furthermore, we examined how the belief that AAPs threaten men’s access to decision-making positions influenced the attribution of these traits to AAP beneficiaries. The results showed that men who reported high levels of perceived threat, as compared to men who reported low levels of perceived threat, attributed more communal than agentic traits to the beneficiaries of quotas. These findings suggest that AAPs may have created a backlash against its beneficiaries by emphasizing gender-stereotypical or counterstereotypical traits. Thus, the framing of AAPs, for instance, as a matter of enhancing organizational performance, in the process of policy making and implementation, may be a crucial tool to countering potential backlash.

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Situational Breakdowns

10.1093/oso/9780190922061.001.0001 ◽

2019 ◽

Cited By ~ 8

Author(s):

Anne Nassauer

Keyword(s):

United States ◽

Large Scale ◽

Contextual Factors ◽

The United States ◽

Social Outcomes ◽

Dynamic Processes ◽

Collective Decisions ◽

Different Types ◽

The Impact

This book provides an account of how and why routine interactions break down and how such situational breakdowns lead to protest violence and other types of surprising social outcomes. It takes a close-up look at the dynamic processes of how situations unfold and compares their role to that of motivations, strategies, and other contextual factors. The book discusses factors that can draw us into violent situations and describes how and why we make uncommon individual and collective decisions. Covering different types of surprise outcomes from protest marches and uprisings turning violent to robbers failing to rob a store at gunpoint, it shows how unfolding situations can override our motivations and strategies and how emotions and culture, as well as rational thinking, still play a part in these events. The first chapters study protest violence in Germany and the United States from 1960 until 2010, taking a detailed look at what happens between the start of a protest and the eruption of violence or its peaceful conclusion. They compare the impact of such dynamics to the role of police strategies and culture, protesters’ claims and violent motivations, the black bloc and agents provocateurs. The analysis shows how violence is triggered, what determines its intensity, and which measures can avoid its outbreak. The book explores whether we find similar situational patterns leading to surprising outcomes in other types of small- and large-scale events: uprisings turning violent, such as Ferguson in 2014 and Baltimore in 2015, and failed armed store robberies.

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A global analysis of the impact of COVID-19 stay-at-home restrictions on crime

Nature Human Behaviour ◽

10.1038/s41562-021-01139-z ◽

2021 ◽

Author(s):

Amy E. Nivette ◽

Renee Zahnow ◽

Raul Aguilar ◽

Andri Ahven ◽

Shai Amram ◽

...

Keyword(s):

Public Space ◽

Global Analysis ◽

Sudden Change ◽

Interrupted Time Series ◽

Urban Crime ◽

Substantial Variation ◽

Different Types ◽

Time Series Analyses ◽

The Impact ◽

At Home

AbstractThe stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.

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Comprehensive Effects of Short-Term Rental Platforms Across Hotel Types in U.S. and International Destinations

Cornell Hospitality Quarterly ◽

10.1177/19389655211033527 ◽

2021 ◽

pp. 193896552110335

Author(s):

John W. O’Neill ◽

Jihwan Yeon

Keyword(s):

Service Providers ◽

Comprehensive Analysis ◽

Competitive Market ◽

Substitution Effects ◽

Short Term ◽

Hotel Performance ◽

The World ◽

Different Types ◽

Location Type ◽

The Impact

In recent years, short-term rental platforms in the lodging sector, including Airbnb, VRBO, and HomeAway, have received extensive attention and emerged as potentially alternative suppliers of services traditionally provided by established commercial accommodation providers, that is, hotels. Short-term rentals have dramatically increased the available supply of rooms for visitors to multiple international destinations, potentially siphoning demand away from hotels to short-term rental businesses. In a competitive market, an increase in supply with constant demand would negatively influence incumbent service providers. In this article, we examine the substitution effects of short-term rental supply on hotel performance in different cities around the world. Specifically, we comprehensively investigate the substitution effects of short-term rental supply on hotel performance based on hotel class, location type, and region. Furthermore, we segment the short-term rental supply based on its types of accommodations, that is, shared rooms, private rooms, and entire homes, and both examine and quantify the differential effects of these types of short-term rentals on different types of hotels. This study offers a comprehensive analysis regarding the impact of multiple short-term rental platforms on hotel performance and offers both conceptual and practical insights regarding the nature and extent of the effects that were identified.

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Double, triple or quadruple hits? Exploring the impact of cybercrime on victims in the Netherlands

International Review of Victimology ◽

10.1177/02697580211010692 ◽

2021 ◽

pp. 026975802110106

Author(s):

Raoul Notté ◽

E.R. Leukfeldt ◽

Marijke Malsch

Keyword(s):

Public Opinion ◽

Literature Review ◽

The Netherlands ◽

Public Discourse ◽

Moral Judgments ◽

Victim Blaming ◽

High Prevalence ◽

Different Types ◽

The Impact ◽

Insight Into

This article explores the impact of online crime victimisation. A literature review and 41 interviews – 19 with victims and 22 with experts – were carried out to gain insight into this. The interviews show that most impacts of online offences correspond to the impacts of traditional offline offences. There are also differences with offline crime victimisation. Several forms of impact seem to be specific to victims of online crime: the substantial scale and visibility of victimhood, victimisation that does not stop in time, the interwovenness of online and offline, and victim blaming. Victims suffer from double, triple or even quadruple hits; it is the accumulation of different types of impact, enforced by the limitlessness in time and space, which makes online crime victimisation so extremely invasive. Furthermore, the characteristics of online crime victimisation greatly complicate the fight against and prevention of online crime. Finally, the high prevalence of cybercrime victimisation combined with the severe impact of these crimes seems contradictory with public opinion – and associated moral judgments – on victims. Further research into the dominant public discourse on victimisation and how this affects the functioning of the police and victim support would be valuable.

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Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽

10.3390/molecules26061497 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1497

Author(s):

Pansong Zhang ◽

Qiao Guo ◽

Zhihua Wei ◽

Qin Yang ◽

Zisheng Guo ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Mammalian Cells ◽

Secretion System ◽

Chinese Herbs ◽

Infection Model ◽

Lung Pathology ◽

Promising Alternative ◽

The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

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Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02001-w ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Zhihui Dou ◽

Dapeng Zhao ◽

Xiaohua Chen ◽

Caipeng Xu ◽

Xiaodong Jin ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Structural Characteristics ◽

Therapy Resistance ◽

Regulatory Elements ◽

Aberrant Splicing ◽

Clinical Role ◽

Splicing Isoforms ◽

The Impact ◽

Splicing Patterns

AbstractBcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

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