Michaelsen Bak (memorybucket1)

Our experiments establish CCRA as a useful tool for quantitative investigations into TF binding and function. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Analysis of ENCODE long RNA-Seq and ChIP-seq (Chromatin Immunoprecipitation Sequencing) datasets for HepG2 and HeLa cell lines uncovered 1647 and 1958 transcripts that interfere with transcription factor binding to human enhancer domains. TFBSs (Transcription Factor Binding Sites) intersected by these 'Enhancer Occlusion Transcripts' (EOTrs) displayed significantly lower relative transcription factor (TF) binding affinities compared to TFBSs for the same TF devoid of EOTrs. Expression of most EOTrs was regulated in a cell line specific manner; analysis for the same TFBSs across cell lines, i.e. in the absence or presence of EOTrs, yielded consistently higher relative TF/DNA-binding affinities for TFBSs devoid of EOTrs. Lower activities of EOTr-associated enhancer domains coincided with reduced occupancy levels for histone tail modifications H3K27ac and H3K9ac. Similarly, the analysis of EOTrs with allele-specific expression identified lower activities for alleles associated with EOTrs. ChIA-PET (Chromatin Interaction Analysis by Paired-End Tag Sequencing) and 5C (Carbon Copy Chromosome Conformation Capture) uncovered that enhancer domains associated with EOTrs preferentially interacted with poised gene promoters. Analysis of EOTr regions with GRO-seq (Global run-on) data established the correlation of RNA polymerase pausing and occlusion of TF-binding. Our results implied that EOTr expression regulates human enhancer domains via transcriptional interference. © The Author(s) 2020. selleck kinase inhibitor Published by Oxford University Press on behalf of Nucleic Acids Research.STUDY OBJECTIVES Intrusive memories of psychological trauma are a core clinical feature of posttraumatic stress disorder (PTSD), and in the early period post-trauma may be a potential target for early intervention. Disrupted sleep in the weeks post-trauma is associated with later PTSD. The impact of sleep and intrusive memories immediately post-trauma, and their relation to later PTSD, is unknown. This study assessed the relationship between sleep duration on the first night following a real-life traumatic event and intrusive memories in the subsequent week, and how these might relate to PTSD symptoms at two months. METHODS Patients (n=87) recruited in the emergency department completed a sleep and intrusive memory diary from the day of their trauma and for the subsequent week, with optional actigraphy. PTSD, anxiety and depression symptoms were assessed at one week and two months. RESULTS A U-shaped relationship was observed between sleep duration on the first night and intrusive memories over the subsequent week sleeping "too little" or "too much" was associated with more intrusive memories. Individuals who met CAPS PTSD criteria at two months had three times more intrusive memories in the first week immediately post-trauma than those who did not (M=28.20 vs. 9.96). Post-hoc analysis showed the absence of intrusive memories in the first week post-trauma was only observed in those who did not meet CAPS criteria for PTSD at two months. CONCLUSIONS Monitoring intrusive memories and sleep in the first week post-trauma, using a simple diary, may help identify individuals more vulnerable to later psychopathology. © Sleep Research Society 2020. Published by Oxford University Press [on behalf of the Sleep Research Society].BACKGROUND In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs. METHODS