Regulatory Architecture of the Neuronal Cacng2/Tarpγ2 Gene Promoter: Multiple Repressive Domains, a Polymorphic Regulatory Short Tandem Repeat, and Bidirectional Organization with Co-regulated lncRNAs

CACNG2 (TARPγ2, Stargazin) is a multi-functional regulator of excitatory neurotransmission and has been implicated in the pathological processes of several brain diseases. Cacng2 function is dependent upon expression level, but currently, little is known about the molecular mechanisms that control expression of this gene. To address this deficit and investigate disease-related gene variants, we have cloned and characterized the rat Cacng2 promoter and have defined three major features: (i) multiple repressive domains that include an array of RE-1 silencing transcription factor (REST) elements, and a calcium regulatory element-binding factor (CaRF) element, (ii) a (poly-GA) short tandem repeat (STR), and (iii) bidirectional organization with expressed lncRNAs. Functional activity of the promoter was demonstrated in transfected neuronal cell lines (HT22 and PC12), but although selective removal of REST and CaRF domains was shown to enhance promoter-driven transcription, the enhanced Cacng2 promoter constructs were still about fivefold weaker than a comparable rat Synapsin-1 promoter sequence. Direct evidence of REST activity at the Cacng2 promoter was obtained through co-transfection with an established dominant-negative REST (DNR) construct. Investigation of the GA-repeat STR revealed polymorphism across both animal strains and species, and size variation was also observed in absence epilepsy disease model cohorts (Genetic Absence Epilepsy Rats, Strasbourg [GAERS] and non-epileptic control [NEC] rats). These data provide evidence of a genotype (STR)-phenotype correlation that may be unique with respect to proximal gene regulatory sequence in the demonstrated absence of other promoter, or 3′ UTR variants in GAERS rats. However, although transcriptional regulatory activity of the STR was demonstrated in further transfection studies, we did not find a GAERS vs. NEC difference, indicating that this specific STR length variation may only be relevant in the context of other (Cacna1h and Kcnk9) gene variants in this disease model. Additional studies revealed further (bidirectional) complexity at the Cacng2 promoter, and we identified novel, co-regulated, antisense rat lncRNAs that are paired with Cacng2 mRNA. These studies have provided novel insights into the organization of a synaptic protein gene promoter, describing multiple repressive and modulatory domains that can mediate diverse regulatory inputs

Evaluation of the relationship between emotional and behavioral problems and quality of life of adolescents in school

Bilgin, sonay/0000-0003-2229-3820WOS: 000502486800001PubMed: 31835908This study was conducted to determine the quality of life and difficulties of adolescents in school age. This descriptive study was conducted in a city center three secondary School. Similarly from each school 114,114,116 people participated in the study, 4 students could not be included in the study due to insufficient data and the study was completed with 344 students. Questionnaire developed by the researcher, the Strengths and Difficulties Questionnaire (SDQ), and the Pediatric Quality of Life Inventory (PedsQL) were used for data collection. Research was completed in line with the ethical principles. According to the evaluations, it was observed that 50.6% of the students was 13 years old, 52% was male, and 53.5% was in the seventh grade. The total score average for PedsQL was 81.58 +/- 13.65, and the mean total score for SDQ was 25.02 +/- 4.813. A positive and significant correlation was found between "behavioral problems" subscale score of the SDQ and all subscales of PedsQL except the "physical health" subscale as well as the positive and significant correlation between the mean total scores of PedsQL and SDQ. It was observed that the quality of life of the students is affected negatively as the difficulties experienced during adolescence increase. Some recommendations were made to reveal the problems experienced by school-age adolescents and to increase their quality of life