Expression of <i>Idh1</i>^R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis

Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis

The biological role of DNA modifications deposited over gene bodies

5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the most common DNA modifications in vertebrate genomes. Promoter-residing 5mC is a well-established transcriptional repression mark. However, the role of gene body DNA modifications, especially those involving 5hmC, remains elusive and controversial. In this study, the role of genic 5mC and 5hmC in transcriptional regulation is investigated. By engineering a cell line with inducible 5hmC it is shown that deposition of 5hmC causes elevated expression of genes with the highest accumulation of this modification. The transcriptional elevating potential of 5hmC is also confirmed via expression analysis of integrated and transfected artificial reporters. Furthermore, it is demonstrated that promoter proximal gene body DNA modifications can modulate transcription initiation in cis. Finally, the ability of methyl-CpG-binding domain protein 1 (MBD1) to interact with genic DNA methylation and repress transcription is analysed. Upon oxidation of 5mC to 5hmC or demethylation, MBD1 binding is abolished and 5mC-mediated repression is relieved. Altogether, this study suggests that 5hmC plays a de-repressive role and proposes a mechanism by which this is achieved.</p

Architectural rhythms in a landscape design

Straipsnyje glaustai apibūdinama architektūros ir želdinių dizaino harmoningo komponavimo principų reikšmė. Esminis principas, apibūdinantis želdynų ir architektūrinio ritmo santykį – tai nuosaikus erdvės mastelio ir formų intervalo suvokimas. Straipsnyje nagrinėjama architektūrinių formų ritminė kaita yra suprantama kaip pastatų, jo architektūrinių detalių ir konstrukcijų seka žmogaus akimis aprėpiamoje erdvėje. Aplinkos harmonija atspindi pastatų ir augalų ritminį išdėstymą. Bendri kompoziciniai vardikliai tarp architektūros ir želdinių formavimo, išreikšti ritmo dėsnių nuostatomis, atskleidžia visumos estetikos svarbą. Rengiant kraštovaizdžio architektūros projektus ir juos įgyvendinant griežtai apibrėžtose teritorijose, pinamos įvairios formų ir ritmo jungtys: pradedant nedideliu gėlynu ar alpinariumu, baigiant skverų ar miesto parkų teritorijomis, kur sprendimo principai kinta pagal erdvės paskirties suvokimą. Straipsnyje pateikiamos ritmo dėsnių schemos bei jų apibrėžimai.This study briefly describes the importance of harmonious composition in architecture and landscape design. The main principle describing the rhythmic relationship between architecture and landscape vegetation is defined by proper interpretation of the scale and rhythmic sequence of forms. In this article we investigate different rhythm patterns of architectural units in a defined space. Application of these findings in landscape design establishes harmony between architecture and greenery. Systemic application of composition theory and, in particular, theory of architectural rhythms in architecture and landscape formation is crucial for establishment of fully functional spaces. In unique landscape design projects (from small flower gardens to city multipurpose parks) that are limited to a well-defined space, different vegetation species and forms together with specific rhythmic patterns, defined by modern composition theory, should be used in order to establish fully functional and aesthetical surroundings. In this study we describe and evaluate several rhythmic schemes and explore their applications in landscape design

MicroRNAs of the miR-290–295 Family Maintain Bivalency in Mouse Embryonic Stem Cells

SummaryNumerous developmentally regulated genes in mouse embryonic stem cells (ESCs) are marked by both active (H3K4me3)- and polycomb group (PcG)-mediated repressive (H3K27me3) histone modifications. This bivalent state is thought to be important for transcriptional poising, but the mechanisms that regulate bivalent genes and the bivalent state remain incompletely understood. Examining the contribution of microRNAs (miRNAs) to the regulation of bivalent genes, we found that the miRNA biogenesis enzyme DICER was required for the binding of the PRC2 core components EZH2 and SUZ12, and for the presence of the PRC2-mediated histone modification H3K27me3 at many bivalent genes. Genes that lost bivalency were preferentially upregulated at the mRNA and protein levels. Finally, reconstituting Dicer-deficient ESCs with ESC miRNAs restored bivalent gene repression and PRC2 binding at formerly bivalent genes. Therefore, miRNAs regulate bivalent genes and the bivalent state itself