21 research outputs found

    Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

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    Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

    Brokering Trust to Enhance Leadership: A Self-Monitoring Approach to Leadership Emergence

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    What kind of person is likely to emerge as an informal leader in the workplace? Experimental research shows that high self-monitors—who tend to adjust their attitudes and behaviors to the demands of different situations—emerge as informal leaders in temporary groups. By contrast, low self-monitors—who tend to be true to themselves in terms of consistency in attitudes and behaviors across different situations—are less likely to emerge as leaders. But this prior research does not address the criticism that the emergence of high self-monitors as leaders represents ephemeral impression management in the context of laboratory experiments. To address this issue, we collected and analyzed data from a 116-member high-technology firm. Our results show that self-monitoring is related not only to leadership emergence, but also to the provision of advice to co-workers. Further, people who occupied brokerage positions (being trusted by those who did not trust each other) tended to be seen as leaders if they were high rather than low self-monitors. From these results, we build a picture of the high self-monitoring emergent leader as someone who notices problems and ameliorates them through the provision of advice and the brokerage of relationships across social divides. The occupation of a structurally advantageous position may well be more advantageous for some (i.e., high self-monitors) relative to others (i.e., low self-monitors)

    Engaging Men as Promotores de Salud: Perceptions of Community Health Workers Among Latino Men in North Carolina

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    The promotor de salud, or community health worker (CHW) role, is highly feminized and little is known about how men view their participation in CHW programs. We conducted in-depth interviews with Latino men in North Carolina to explore this gap. We used systematic coding and display procedures informed by Grounded Theory to analyze the data. Men described their communities as lacking cohesion, making integration of Latino immigrants difficult. Most did not consider themselves leaders or feel they had leaders in their communities. Their perceptions of the feminized CHW role as well as the volunteer or low-paid nature of CHW work conflicted with men’s provider role. They also did not think they could perform the CHW role because they lacked education, skills, and broad networks. Efforts to increase male participation in CHW programs in new Latino immigrant destinations will need to understand and address these gender and migration-related dynamics in order to engage both women and men in improving the health of their communities

    Type A and type behaviors and factors related to job satisfaction among male white-collar workers

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    Numerous studies have examined the health effects of Type A behavior and job satisfaction/dissatisfaction, but we know very little about the relationship between aspects of the work environment related to job satisfaction and the Type A behavior pattern. In the present study, we analyzed data concerning work Stressors, private aspects of life, and job satisfaction among male white-collar workers (n=657) in a large steel company, and identified the respective aspects of the work environment related to job satisfaction among groups divided by Type A/B behavior patterns
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