Quantifying Eukaryotic Gene Regulation in Hormone Response and Disease.

Quantifying the function of mammalian enhancers at the genome or population scale has been longstanding challenge in the field of gene regulation. Studies of individual enhancers have provided anecdotal evidence on which many foundational assumptions in the field are based. Genome-scale studies have revealed that the number of sites bound by a given transcription factor far outnumber the genes that the factor regulates. In this dissertation we describe a new method, chromatin immune-enriched reporter assays (ChIP-reporters), and use that approach to comprehensively test the enhancer activity of genomic loci bound by the glucocorticoid receptor (GR). Integrative genomics analyses of our ChIP-reporter data revealed an unexpected mechanism of glucocorticoid (GC)-induced gene regulation. In that mechanism, only the minority of GR bound sites acts as GC-inducible enhancers. Many non-GC-inducible GR binding sites interact with GC-induced sites via chromatin looping. These interactions can increase the activity of GC-induced enhancers. Finally, we describe a method that enables the detection and characterization of the functional effects of non-coding genetic variation on enhancer activity at the population scale. Taken together, these studies yield both mechanistic and genetic evidence that provides context that informs the understanding of the effects of multiple enhancer variants on gene expression.

Barriers to reporting child maltreatment: do emergency medical services professionals fully understand their role as mandatory reporters?

BACKGROUND: Child maltreatment is underreported in the United States and in North Carolina. In North Carolina and other states, mandatory reporting laws require various professionals to make reports, thereby helping to reduce underreporting of child maltreatment. This study aims to understand why emergency medical services (EMS) professionals may fail to report suspicions of maltreatment despite mandatory reporting policies. METHODS: A web-based, anonymous, voluntary survey of EMS professionals in North Carolina was used to assess knowledge of their agency's written protocols and potential reasons for underreporting suspicion of maltreatment (n=444). Results were based on descriptive statistics. Responses of line staff and leadership personnel were compared using chi-square analysis. RESULTS: Thirty-eight percent of respondents were unaware of their agency's written protocols regarding reporting of child maltreatment. Additionally, 25% of EMS professionals who knew of their agency's protocol incorrectly believed that the report should be filed by someone other than the person with firsthand knowledge of the suspected maltreatment. Leadership personnel generally understood reporting requirements better than did line staff. Respondents indicated that peers may fail to report maltreatment for several reasons: they believe another authority would file the report, including the hospital (52.3%) or law enforcement (27.7%); they are uncertain whether they had witnessed abuse (47.7%); and they are uncertain about what should be reported (41.4%). LIMITATIONS: This survey may not generalize to all EMS professionals in North Carolina. CONCLUSIONS: Training opportunities for EMS professionals that address proper identification and reporting of child maltreatment, as well as cross-agency information sharing, are warranted.