Biology subjects

Roeh, S.

Publications and source records attributed to Roeh, S..

3 recordsLinked to original sources

bioRxiv2018

Identity domains in complex behavior: Toward a biology of personality

Personality traits offer considerable insight into the biological basis of individual differences. However, existing approaches toward understanding personality across species rely on subjective criteria and limited sets of behavioral readouts, resulting in noisy and often inconsistent outcomes. Here, we introduce a mathematical framework for studying individual differences along dimensions with maximum consistency and discriminative power. We validate this framework in mice, using data from a system for high-throughput longitudinal monitoring of group-housed mice that yields a variety of readouts from all across an individuals behavioral repertoire. We describe a set of stable traits that capture variability in behavior and gene expression in the brain, allowing for better informed mechanistic investigations into the biology of individual differences.

animal behavior and cognition↗

bioRxiv2017

The role of m6A-RNA methylation in stress response regulation

N6-Methyladenosine (m6A) is an abundant internal RNA modification that regulates transcript processing and translation. The regulation of brain m6A by stressful stimuli in vivo and its role in the stress response are currently unknown.\n\nHere, we provide a detailed analysis of the stress-epitranscriptome using m6A-Seq, global and gene-specific m6A measurements. We show that stress exposure and glucocorticoids alter m6A and its regulatory network in a region- and time-specific manner. We demonstrate that depletion of the methyltransferase Mettl3 and the demethylase Fto in adult neurons increases fear memory, and alters the transcriptome response to fear as well as synaptic plasticity. Finally, we report that regulation of m6A is impaired in major depressive disorder patients following glucocorticoid receptor activation.\n\nOur findings indicate that brain m6A represents a novel layer of complexity in gene expression regulation after stress and that dysregulation of the m6A-response may contribute to the pathophysiology of stress-related psychiatric disorders.\n\nHighlightsO_LIm6A RNA methylation in adult mouse brain is regulated by stress\nC_LIO_LIBrain m6A levels are temporally and spatially regulated by stress\nC_LIO_LIMettl3 and Fto-KO alter fear memory, transcriptome response and synaptic plasticity\nC_LIO_LIThe m6A-glucocorticoid-response is impaired in major depressive disorder patients\nC_LI\n\neTOC blurbEngel et al. demonstrate a brain-area-specific and time-dependent role for the mRNA modification, m6A, in stress-response regulation. Manipulating m6A-enzymes alters fear-memory, transcriptome-response and synaptic-plasticity. Altered m6A dynamics in depressed patients suggest an involvement of m6A-modifications in stress-related psychiatric disorders.

neuroscience↗

bioRxiv2017

HAM-TBS: High accuracy methylation measurements via targeted bisulfite sequencing

BackgroundThe ability to accurately and efficiently measure DNA methylation is vital to advance the understanding of this mechanism and its contribution to common diseases. Here, we present a highly accurate method to measure methylation using bisulfite sequencing (termed HAM-TBS). This novel method is able to assess DNA methylation in multiple samples with high accuracy in a cost-effective manner. We developed this assay for the FKBP5 locus, an important gene in the regulation of the stress system and previously linked to stress-related disorders, but the method is applicable to any locus of interest.\n\nResultsHAM-TBS enables multiplexing of up to 96 samples spanning a region of ~10 kb using the llumina MiSeq. It incorporates a triplicate bisulfite conversion step, pooled target enrichment via PCR, PCR-free library preparation and a minimum coverage of 1,000x. Furthermore, we designed and validated a targeted panel to specifically assess regulatory regions within the FKBP5 locus including the transcription start site, topologically associated domain boundaries, intergenic and proximal enhancers as well as glucocorticoid receptor and CTCF binding sites that are not covered in commercially available DNA methylation arrays.\n\nConclusionsHAM-TBS represents a highly accurate, medium-throughput sequencing approach for robust detection of DNA methylation changes in specific target regions.

genetics↗