Altered copy number of certain highly repetitive regions of the genome, such as satellite DNA within heterochromatin and ribosomal RNA loci (rDNA), is hypothesized to help safeguard the genome against damage derived from external stressors. We quantified copy number of the 18S rDNA and a pericentromeric satellite DNA (Msat-160) in bank voles (Myodes glareolus) inhabiting the Chernobyl Exclusion Zone (CEZ), an area that is contaminated by radionuclides and where organisms are exposed to elevated levels of ionizing radiation. We found a significant increase in 18S rDNA and Msat-160 content in the genomes of bank voles from contaminated locations within the CEZ compared with animals from uncontaminated locations. Moreover, 18S rDNA and Msat-160 copy number were positively correlated in the genomes of bank voles from uncontaminated, but not in the genomes of animals inhabiting contaminated, areas. These results show the capacity for local-scale geographic variation in genome architecture and are consistent with the genomic safeguard hypothesis. Disruption of cellular processes related to genomic stability appears to be a hallmark effect in bank voles inhabiting areas contaminated by radionuclides.

• Keywords
• anthropogenic disturbance, chernobyl, copy number, ionizing radiation, myodes glareolus, rDNA,
• Publication type
• Journal Article MeSH

Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1-deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro-differentiation was almost suppressed. Neuro-differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia-like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenia-like brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that co-regulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro-differentiation as well as the pathophysiology of a schizophrenia-like phenotype.

• Keywords
• H3K9 acetylation, HDACs, acetylome, mouse neurogenesis, schizophrenia,
• MeSH
• Acetylation MeSH
• Cannabinoid Receptor Antagonists pharmacology   MeSH
• Antipsychotic Agents pharmacology   MeSH
• Time Factors MeSH
• Epigenesis, Genetic MeSH
• Gestational Age MeSH
• Histone Deacetylase 1 antagonists & inhibitors   genetics   metabolism   MeSH
• Histone Deacetylases genetics   metabolism   MeSH
• Histones metabolism   MeSH
• Histone Deacetylase Inhibitors pharmacology   MeSH
• Methylazoxymethanol Acetate MeSH
• Disease Models, Animal MeSH
• Neural Cell Adhesion Molecules genetics   metabolism   MeSH
• Brain drug effects   embryology   enzymology   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Neurogenesis * drug effects   MeSH
• Neurons drug effects   enzymology   pathology   MeSH
• Protein Processing, Post-Translational MeSH
• Rats, Sprague-Dawley MeSH
• Receptor, Cannabinoid, CB1 antagonists & inhibitors   metabolism   MeSH
• Schizophrenia chemically induced   drug therapy   enzymology   genetics   MeSH
• Signal Transduction MeSH
• SOXB1 Transcription Factors genetics   metabolism   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cannabinoid Receptor Antagonists MeSH
• Antipsychotic Agents MeSH
• Cnr1 protein, rat MeSH Browser
• Hdac1 protein, mouse MeSH Browser
• Hdac1 protein, rat MeSH Browser
• Histone Deacetylase 1 MeSH
• Histone Deacetylases MeSH
• histone deacetylase 3 MeSH Browser
• Histones MeSH
• Histone Deacetylase Inhibitors MeSH
• Methylazoxymethanol Acetate MeSH
• Neural Cell Adhesion Molecules MeSH
• Receptor, Cannabinoid, CB1 MeSH
• Sox2 protein, mouse MeSH Browser
• SOXB1 Transcription Factors MeSH

Cajal bodies (CBs) are important compartments containing accumulated proteins that preferentially regulate RNA-related nuclear events, including splicing. Here, we studied the nuclear distribution pattern of CBs in neurogenesis. In adult brains, coilin was present at a high density, but CB formation was absent in the nuclei of the choroid plexus of the lateral ventricles. Cells of the adult hippocampus were characterized by a crescent-like morphology of coilin protein. We additionally observed a 70 kDa splice variant of coilin in adult mouse brains, which was different to embryonic brains and mouse pluripotent embryonic stem cells (mESCs), characterized by the 80 kDa standard variant of coilin. Here, we also showed that depletion of coilin is induced during neural differentiation and HDAC1 deficiency in mESCs caused coilin accumulation inside the fibrillarin-positive region of the nucleoli. A similar distribution pattern was observed in adult brain hippocampi, characterized by lower levels of both coilin and HDAC1. In summary, we observed that neural differentiation and HDAC1 deficiency lead to coilin depletion and coilin accumulation in body-like structures inside the nucleoli.

• Publication type
• Journal Article MeSH

DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I- PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I- PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, γH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I- PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps.

• Keywords
• CARM1, DNA repair, HDAC1, NBS1, PpoI, chromatin, nucleolus,
• MeSH
• Acetylation MeSH
• Arginine metabolism   MeSH
• Cell Nucleolus genetics   ultrastructure   MeSH
• Cell Line MeSH
• DNA Breaks, Double-Stranded * MeSH
• Embryonic Stem Cells metabolism   ultrastructure   MeSH
• Phosphoproteins metabolism   MeSH
• Genes, rRNA MeSH
• Histone Deacetylase 1 metabolism   MeSH
• Histones metabolism   MeSH
• Intracellular Signaling Peptides and Proteins MeSH
• Nuclear Proteins metabolism   MeSH
• Methylation MeSH
• Mice MeSH
• DNA Repair MeSH
• Protein-Arginine N-Methyltransferases metabolism   MeSH
• RNA, Ribosomal genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Arginine MeSH
• coactivator-associated arginine methyltransferase 1 MeSH Browser
• Phosphoproteins MeSH
• Hdac1 protein, mouse MeSH Browser
• Histone Deacetylase 1 MeSH
• Histones MeSH
• Intracellular Signaling Peptides and Proteins MeSH
• Nuclear Proteins MeSH
• Protein-Arginine N-Methyltransferases MeSH
• RNA, Ribosomal MeSH
• Tcof1 protein, mouse MeSH Browser