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Shaping the cellular landscape with Set2/SETD2 methylation
Chromatin structure is a major barrier to gene transcription that must be disrupted and re-set during each round of transcription. Central to this process is the Set2/SETD2 methyltransferase that mediates co-transcriptional methylation to histone H3 at lysine 36 (H3K36me). Studies reveal that H3K36me not only prevents inappropriate transcriptional initiation from arising within gene bodies, but that it has other conserved functions that include the repair of damaged DNA and regulation of pre-mRNA splicing. Consistent with the importance of Set2/SETD2 in chromatin biology, mutations of SETD2, or mutations at or near H3K36 in H3.3, have recently been found to underlie cancer development. This review will summarize the latest insights into the functions of Set2/SETD2 in genome regulation and cancer development.
Journal Article
Tissue-Specific DNA Replication Defects in Drosophila melanogaster Caused by a Meier-Gorlin Syndrome Mutation in Orc4
Abstract
Meier-Gorlin syndrome (MGS) is a recessive disorder caused by mutations in genes associated with DNA replication. Despite the fact these proteins are essential for replication in every cell, patients with MGS have tissue-specific defects...
Meier-Gorlin syndrome is a rare recessive disorder characterized by a number of distinct tissue-specific developmental defects. Genes encoding members of the origin recognition complex (ORC) and additional proteins essential for DNA replication (CDC6, CDT1, GMNN, CDC45, MCM5, and DONSON) are mutated in individuals diagnosed with MGS. The essential role of ORC is to license origins during the G1 phase of the cell cycle, but ORC has also been implicated in several nonreplicative functions. Because of its essential role in DNA replication, ORC is required for every cell division during development. Thus, it is unclear how the Meier-Gorlin syndrome mutations in genes encoding ORC lead to the tissue-specific defects associated with the disease. To begin to address these issues, we used Cas9-mediated genome engineering to generate a Drosophila melanogaster model of individuals carrying a specific Meier-Gorlin syndrome mutation in ORC4 along with control strains. Together these strains provide the first metazoan model for an MGS mutation in which the mutation was engineered at the endogenous locus along with precisely defined control strains. Flies homozygous for the engineered MGS allele reach adulthood, but with several tissue-specific defects. Genetic analysis revealed that this Orc4 allele was a hypomorph. Mutant females were sterile, and phenotypic analyses suggested that defects in DNA replication was an underlying cause. By leveraging the well-studied Drosophila system, we provide evidence that a disease-causing mutation in Orc4 disrupts DNA replication, and we propose that in individuals with MGS defects arise preferentially in tissues with a high-replication demand.
Journal Article
An investigation of match-up effects in sport sponsorship advertising: The implications of consumer advertising schemas
Statistics show that sponsorship of sports and other events is one of the fastest growing areas of promotion (Ukman, 1995), but the importance of this persuasion strategy is not reflected in the amount of attention it has received in the marketing literature. Although some research has been done in this area, the majority of work has not employed the same theoretical and methodological rigor given other areas of consumer behavior (Cunningham & Taylor, 1995). Some scholars (e.g., Gwinner, 1997; Keller, 1993) have suggested that sponsorship functions like celebrity endorser advertising, where the perceived match (or mismatch) of brand attributes with the endorser's attributes influences consumer response to such marketing communications. One of the theoretical rationales used to explain matchup effects in endorser advertising is a schema‐based information processing paradigm (Lynch & Schuler, 1994; Misra & Beatty, 1990). The purpose of the current study was to examine the notion that consumers possess schemas that influence their reactions to advertising leveraging sport sponsorships. The research utilizes a 3 × 2 × 2 factorial design, where three variations of sport sponsorship print ads and two different magazine covers (sport and nonsport) are used to test the influence of brand/event matchups and advertising placement on intermediate measures of advertising effectiveness. In addition to matchup and media vehicle effects, differential response by gender is also examined. Three hypotheses are tested based on research from the literature on sponsorship, matchup effects, and advertising schemas. MANOVA results provide partial support for all three hypotheses, as matchup and media vehicle manipulations were found to significantly impact Aad. Moreover, females are found to report significantly higher Aad and Pi than did males in this study. The advertising schema framework is used to discuss the research findings. This discussion deals with the work's applied and theoretical implications and its limitations, as well as directions for future studies on sponsorship. © 1999 John Wiley & Sons, Inc.
Journal Article
DRH1 , a p68-related RNA helicase gene , is required for chromosome breakage in Tetrahymena
The p68 DEAD box helicases comprise a widely conserved protein family involved in a large range of biological processes including transcription, splicing and translation. The genome of the ciliate Tetrahymena thermophile encodes two p68-like helicases, Drh1p and Lia2p. We show that DRH1 is essential for growth and completion of development. In growing cells, Drh1p is excluded from the nucleus and accumulates near cortical basal bodies. In contrast, during sexual reproduction, this protein localizes to meiotic micronuclei, initially in punctate foci in regions where centromeres and telomeres are known to reside and later in post-zygotic differentiating somatic macronuclei. Differentiation of the macronuclear genome involves extensive DNA rearrangements including fragmentation of the five pairs of germline-derived chromosomes into 180 chromosomal sub-fragments that are stabilized by de novo telomere deletion. In addition, thousands of internal eliminated sequences (IESs) are excised from loci dispersed throughout the genome. Strains with DRH1 deleted from the germline nuclei, which do not express the protein during post-zygotic development, fail to fragment the developing macronuclear chromosomes. IES excision still occurs in the absence of DRH1 zygotic expression; thus, Drh1p is the first protein found to be specifically required for chromosome breakage but not DNA elimination.
Journal Article
The implications of recency and gender effects in consumer response to ambush marketing
So‐called ambush marketers, are companies that use clever advertising imagery (and/or ad placement) to link their brand(s) with a major event, in the minds of its audience, without having to purchase the expensive rights fees that event properties often charge for official sponsorship status. This study uses an experimental design to explore certain effects of the ambush marketing strategy. Its focus is on the potential impact of recency (of ad exposure), as well as gender differences, on measures of memory, brand attitude, and behavioral intentions for brands perceived to be official sponsors. Respondents (n‐215) were randomly assigned to groups viewing Olympics programming intercut with advertising for either official sponsors or ambush marketers. No statistically significant differences are observed between males and females in their pretest sponsor recall or recognition levels, whereas recency of ad exposure is found to be a significant influence on posttest sponsor awareness in the aggregate. Significant gender differences are detected, however, in attitude toward the brand and purchase intentions for two of three product categories investigated, as females have higher mean scores for those two measures. The implications of these results are discussed and followed by recommendations for event promoters seeking to preserve the value of event sponsorships, along with defensive advertising‐strategies to protect the investments of their official sponsors. © 1998 John Wiley & Sons, Inc.
Journal Article
INVESTIGATING THE ROLES OF GAMBLING INTEREST AND IMPULSIVE SENSATION SEEKING ON CONSUMER ENJOYMENT OF PROMOTIONAL GAMES
Promotional games are an increasingly utilized form of sales promotion; yet, few studies exist in this area. Some research suggests that promotional game participants may be similar to gamblers in terms of lifestyles and personality traits, such as sensation seeking. The current study
extends existing research on this topic, by utilizing a telephone survey of randomly selected adults from two major cities in the U.S. (N=555), to examine this notion. Results support the similarity between promotional game participants and gamblers. Respondents' race, gambling
interest levels, variety of gambling activities and sensation seeking are all found to be associated with liking to participate in promotional games.
Journal Article
The Relationship Between Sexual Orientation and Risk for Suicide: Research Findings and Future Directions for Research and Prevention
This article reviews evidence for a link between suicide or suicidal behavior and sexual orientation by: 1) reviewing studies of the rates of completed and attempted suicide for gay, lesbian and bisexual people compared to the general population; 2) examining possible risk factors; 3) outlining opportunities for prevention; and 4) providing directions for future research. (BF)
Journal Article
Strategic green marketing
Argues that \"Green Marketing\" is taking shape as one of
the key business strategies of the future, and that the increasing
environmental consciousness makes it incumbent on consumer marketers not
just to respond to it, but to lead the way in environmental programs.
Sets forth the need and recommendations for incorporating environmental
concerns into strategic marketing planning of the organisation.
Journal Article