[Serotonergic genes in the development of anxiety/depression-like state and pathology of aggressive behavior in male mice: RNA-seq data].

In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.

[Changes in the Expression of Dopaminergic Genes in Brain Structures of Male Mice Exposed to Chronic Social Defeat Stress: An RNA-seq Study].

Whole-transcriptome analysis (RNA-seq) has been used to analyze changes in the expression of dopaminergic genes that encode proteins involved in the synthesis, inactivation, and neurotransmission of dopamine in the striatum, ventral tegmental area, raphe nuclei of the midbrain, hypothalamus, and hippocampus of male mice subjected to chronic social defeat. The expression of Th, Ddc, and Slc6A3 (Dat1) was upregulated, while that of Ppp1r1b and Sncg was downregulated in the ventral tegmental area; the expression of Th, Ddc, Drd2, and Sncg was downregulated in the raphe nuclei of midbrain; the expression of Th, Aldh2, and Ppp1r1b was upregulated, while that of Маоа was downregulated in the hypothalamus; Drd1 and Snca expression was downregulated and that of Sncb was upregulated in the striatum, and Sncb expression was upregulated in the hippocampus. There were no statistically significant changes in the expression of Comt, Maob, Drd3, Drd4, or Drd5 in the brain areas analyzed in stressed male mice (compared to control animals). Thus, the number of differentially expressed dopaminergic genes and the direction of expression changes in male mice experiencing chronic stress are specific to regions of the brain.

[Regulatory Genomics: Integrated Experimental and Computer Approaches].

The review describes integrated experimental and computer approaches to the investigation of the mechanisms of transcriptional regulation of the organization of eukaryotic genes and transcription regulatory regions. These include (a) an analysis of the factors affecting the affinity of TBP (TATA-binding protein) for the TATA box; (b) research on the patterns of chromatin mark distributions and their role in the regulation of gene expression; (c) a study of 3D chromatin organization; (d) an estimation of the effects of polymorphisms on gene expression via high-resolution Chip-seq and DNase-seq techniques. It was demonstrated that integrated experimental and computer approaches are very important for the current understanding of transcription regulatory mechanisms and the structural and functional organization of the regulatory regions controlling transcription.

Translation efficiency in yeasts correlates with nucleosome formation in promoters.

Elongation efficiency index (EEI) was suggested earlier to estimate gene expression efficiency by nucleotide context of coding sequence in unicellular organisms. We have analyzed association between EEI and nucleosome formation potential (NFP) in 5' regulatory regions upstream translation initiation site (TIS) from two yeast species. Theoretical estimations of NFP based on DNA sequence were obtained by Recon method. Experimental estimation of nucleosome occupancy was obtained by high-throughput sequencing data of nucleosomal DNA in Saccharomyces cerevisiae . For the sample of all genes correlation coefficient was calculated between two vectors: vector of NFP values for fixed position relative to TIS and vector of EEI values. Profiles of correlation coefficients of NFP and EEI were counted in (-600; +600) regions relative to TIS for gene sequences extracted from GenBank. We found regions of strong negative dependence between NFP and EEI for all genes as well as for 10% highly expressed genes in Schizosaccharomyces pombe (10% of EEI-highest genes). At the same time, we found positive dependence between NFP and EEI for all genes and for low expressed genes in S. cerevisiae (10% of EEI-lowest genes). The association between NFP and EEI could be explained by evolutionary selection of context characteristics of nucleotide sequences for gene expression optimization.