46 research outputs found
The role of Prdm9 in the house mouse hybrid sterility model
No full text(English) Hybrid sterility is a phenomenon representing reproductive isolation between closely related species and thus assuring the process of speciation. Hybrid sterility is a complex polygenic trait and the most significant advance in its study is achieved in Drosophila melanogaster. Nearly half century ago Forejt and Ivanyi mapped the first hybrid sterility genetic locus in vertebrates (Hybrid sterility 1, Hst1) in crosses of wild mice with laboratory inbred strains where the male offspring is sterile. Further mapping of the locus led to discovery of a gene called PR domain zinc finger protein 9 (Prdm9), a histone methyltransferase, whose deficiency causes meiotic arrest and sterility in mice. Furthermore, it was found that Prdm9 defines the hotspot placement in meiotic recombination by posting trimethylation marks on lysine residues 4 and 36 of histone 3 hence explaining the observed defects in its absence during meiosis. Nonetheless, its exact role in molecular mechanism of hybrid sterility is yet unclear. Prdm9 expression is present during the stage of formation of meiotic DNA double-strand breaks and is a hint about the time of hybrid sterility initiation. Phenotypically in the case of male mouse hybrid sterility is observed incomplete chromosome synapsis, meiotic arrest at mid-to-late..
Role Prdm9 v modelu hybridní sterility myši domácí
No full text(česky) Hybridní sterilita je fenomén představující reprodukční izolaci mezi blízce příbuznými druhy a tím zajištění procesu speciace. Hybridní sterilita je komplexní polygenní znak a nejvýznamnějšího pokroku v jejím studiu je dosaženo u Drosophila melanogaster. Před téměř půlstoletím Forejt a Ivanyi zmapovali první genetický lokus hybridní sterility u obratlovců (Hybrid sterility 1, Hst1) u křížení divokých myší s laboratorními inbredními kmeny, kde je samčí potomek sterilní. Další mapování lokusu vedlo k objevu genu zvaného PR doména zinc finger protein 9 (Prdm9), histon methyltransferáza, jejíž nedostatek způsobuje meiotické zastavení a sterilitu u myší. Dále bylo zjištěno, že Prdm9 definuje umístění hotspotu v meiotické rekombinaci umístěním trimethylačních značek na lysinové zbytky 4 a 36 histonu 3, což vysvětluje pozorované defekty v jeho nepřítomnosti během meiózy. Nicméně jeho přesná role v molekulárním mechanismu hybridní sterility je zatím nejasná. Exprese Prdm9 je přítomna během fáze tvorby dvouřetězcových zlomů meiotické DNA a je náznakem doby iniciace hybridní sterility. Fenotypicky v případě hybridní sterility samců myší je pozorována neúplná chromozomová synapse, meiotická zástava ve střední až pozdní fázi pachytenu, transkripční dereprese chromozomu X, menší varlata a nedostatek...(English) Hybrid sterility is a phenomenon representing reproductive isolation between closely related species and thus assuring the process of speciation. Hybrid sterility is a complex polygenic trait and the most significant advance in its study is achieved in Drosophila melanogaster. Nearly half century ago Forejt and Ivanyi mapped the first hybrid sterility genetic locus in vertebrates (Hybrid sterility 1, Hst1) in crosses of wild mice with laboratory inbred strains where the male offspring is sterile. Further mapping of the locus led to discovery of a gene called PR domain zinc finger protein 9 (Prdm9), a histone methyltransferase, whose deficiency causes meiotic arrest and sterility in mice. Furthermore, it was found that Prdm9 defines the hotspot placement in meiotic recombination by posting trimethylation marks on lysine residues 4 and 36 of histone 3 hence explaining the observed defects in its absence during meiosis. Nonetheless, its exact role in molecular mechanism of hybrid sterility is yet unclear. Prdm9 expression is present during the stage of formation of meiotic DNA double-strand breaks and is a hint about the time of hybrid sterility initiation. Phenotypically in the case of male mouse hybrid sterility is observed incomplete chromosome synapsis, meiotic arrest at mid-to-late...Katedra genetiky a mikrobiologieDepartment of Genetics and MicrobiologyPřírodovědecká fakultaFaculty of Scienc
Corrigendum: Ethnopharmacological Approaches for Therapy of Jaundice: Part II. Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae, Combretaceae, and Fabaceae Families
No full textNo abstract available© 2017 Tewari, Mocan, Parvanov, Sah, Nabavi, Huminiecki, Ma, Lee, Horbańczuk and Atanaso
A quantitative assay for crossover and noncrossover molecular events at individual recombination hotspots in both male and female gametes
No full textAbstractMeiotic recombination is a fundamental process in all eukaryotes. Among organisms in which recombination initiates prior to synapsis, recombination preferentially occurs in short 1-to 2-kb regions, known as recombination hotspots. Among mammals, genotyping sperm DNA has provided a means of monitoring recombination events at specific hotspots in male meiosis. To complement these current techniques, we developed an assay for amplifying all copies of a hotspot from the DNA of male and female germ cells, cloning the products into Escherichia coli, and SNP genotyping the resulting colonies using fluorescence technology. This approach examines the molecular details of crossover and noncrossover events of individual meioses directly at active hotspots while retaining the simplicity of using pooled DNA. Using this technique, we analyzed recombination events at the Hlx1 hotspot located on mouse chromosome 1, finding that the results agree well with a prior genetic characterization of 3026 male and 3002 female meioses
Trans-regulation of mouse meiotic recombination hotspots by Rcr1.
No full textMeiotic recombination is required for the orderly segregation of chromosomes during meiosis and for providing genetic diversity among offspring. Among mammals, as well as yeast and higher plants, recombination preferentially occurs at highly delimited chromosomal sites 1-2 kb long known as hotspots. Although considerable progress has been made in understanding the roles various proteins play in carrying out the molecular events of the recombination process, relatively little is understood about the factors controlling the location and relative activity of mammalian recombination hotspots. To search for trans-acting factors controlling the positioning of recombination events, we compared the locations of crossovers arising in an 8-Mb segment of a 100-Mb region of mouse Chromosome 1 (Chr 1) when the longer region was heterozygous C57BL/6J (B6) x CAST/EiJ (CAST) and the remainder of the genome was either similarly heterozygous or entirely homozygous B6. The lack of CAST alleles in the remainder of the genome resulted in profound changes in hotspot activity in both females and males. Recombination activity was lost at several hotspots; new, previously undetected hotspots appeared; and still other hotspots remained unaffected, indicating the presence of distant trans-acting gene(s) whose CAST allele(s) activate or suppress the activity of specific hotspots. Testing the activity of three activated hotspots in sperm samples from individual male progeny of two genetic crosses, we identified a single trans-acting regulator of hotspot activity, designated Rcr1, that is located in a 5.30-Mb interval (11.74-17.04 Mb) on Chr 17. Using an Escherichia coli cloning assay to characterize the molecular products of recombination at two of these hotspots, we found that Rcr1 controls the appearance of both crossover and noncrossover gene conversion events, indicating that it likely controls the sites of the double-strand DNA breaks that initiate the recombination process
Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)
No full textPRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) (PR) homologous domain containing (PRDM) transcription factors are expressed in neuronal and stem cell systems, and they exert multiple functions in a spatiotemporal manner. Therefore, it is believed that PRDM factors cooperate with a number of protein partners to regulate a critical set of genes required for maintenance of stem cell self-renewal and differentiation through genetic and epigenetic mechanisms. In this review, we summarize recent findings about the expression of PRDM factors and function in stem cell and neuronal systems with a focus on cofactor-dependent regulation of PRDM3/16 and FOG1/2. We put special attention on summarizing the effects of the PRDM proteins interaction with chromatin modulators (NuRD complex and CtBPs) on the stem cell characteristic and neuronal differentiation. Although PRDM factors are known to possess intrinsic enzyme activity, our literature analysis suggests that cofactor-dependent regulation of PRDM3/16 and FOG1/2 is also one of the important mechanisms to orchestrate bidirectional target gene regulation. Therefore, determining stem cell and neuronal-specific cofactors will help better understanding of PRDM3/16 and FOG1/2-controlled stem cell maintenance and neuronal differentiation. Finally, we discuss the clinical aspect of these PRDM factors in different diseases including cancer. Overall, this review will help further sharpen our knowledge of the function of the PRDM3/16 and FOG1/2 with hopes to open new research fields related to these factors in stem cell biology and neuroscience
Ethnopharmacological Approaches for Therapy of Jaundice: Part II. Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae, Combretaceae, and Fabaceae Families
No full textIn many developing countries, jaundice is the common symptom of hepatic diseases which are a major cause of mortality. The use of natural product-based therapies is very popular for such hepatic disorders. A great number of medicinal plants have been utilized for this purpose and some facilitated the discovery of active compounds which helped the development of new synthetic drugs against jaundice. However, more epidemiological studies and clinical trials are required for the practical implementation of the plant pharmacotherapy of jaundice. The focus of this second part of our review is on several of the most prominent plants used against jaundice identified in the analysis performed in the first part of the review viz. Andrographis paniculata (Burm.f.) Nees, Silybum marianum (L.) Gaertn., Terminalia chebula Retz., Glycyrrhiza glabra L. and some species of genus Phyllanthus. Furthermore, we discuss their physiological effects, biologically active ingredients, and the potential mechanisms of action. Some of the most important active ingredients were silybin (also recommended by German commission), phyllanthin and andrographolide, whose action leads to bilirubin reduction and normalization of the levels of relevant serum enzymes indicative for the pathophysiological status of the liver.© 2017 Tewari, Mocan, Parvanov, Sah, Nabavi, Huminiecki, Ma, Lee, Horbańczuk and Atanaso
Ethnopharmacological Approaches for Therapy of Jaundice: Part I
No full textJaundice is a very common symptom especially in the developing countries. It is associated with several hepatic diseases which are still major causes of death. There are many different approaches to jaundice treatment and the growing number of ethnomedicinal studies shows the plant pharmacology as very promising direction. Many medicinal plants are used for the treatment of jaundice, however a comprehensive review on this subject has not been published. The use of medicinal plants in drug discovery is highly emphasized (based on their traditional and safe uses in different folk medicine systems from ancient times). Many sophisticated analytical techniques are emerging in the pharmaceutical field to validate and discover new biologically active chemical entities derived from plants. Here, we aim to classify and categorize medicinal plants relevant for the treatment of jaundice according to their origin, geographical location, and usage. Our search included various databases like Pubmed, ScienceDirect, Google Scholar. Keywords and phrases used for these searches included: “jaundice,” “hyperbilirubinemia,” “serum glutamate,” “bilirubin,” “Ayurveda.” The first part of the review focuses on the variety of medicinal plant used for the treatment of jaundice (a total of 207 medicinal plants). In the second part, possible mechanisms of action of biologically active secondary metabolites of plants from five families for jaundice treatment are discussed.© 2017 Tewari, Mocan, Parvanov, Sah, Nabavi, Huminiecki, Ma, Lee, Horbańczuk and Atanaso
DNA binding specificities of the long zinc-finger recombination protein PRDM9
No full textBACKGROUND: Meiotic recombination ensures proper segregation of homologous chromosomes and creates genetic variation. In many organisms recombination occurs at limited sites, termed hotspots, whose positions in mammals are determined by PRDM9, a long array zinc finger and chromatin modifier protein. Determining the rules governing the DNA binding of PRDM9 is a major issue in understanding how it functions. RESULTS: We show that mouse PRDM9 protein variants bind hotspot DNA sequences in a manner that is specific for both PRDM9 and DNA haplotype and that in vitro binding parallels in vivo biological activity. Examining four hotspots, three activated by Prdm9Cst and one activated by Prdm9Dom2, we found that all binding sites required the full array of 11 or 12 contiguous fingers, depending on the allele, and that there was little sequence similarity between the binding sites of the three Prdm9Cst activated hotspots. The binding specificity of each position in the Hlx1 binding site, activated by Prdm9Cst, was tested by mutating each nucleotide to its three alternatives. The 31 positions along the binding site varied considerably in the ability of alternative bases to support binding, which also implicates a role for additional binding to the DNA phosphate backbone. CONCLUSIONS: These results, which provide the first detailed mapping of PRDM9-DNA binding and, to our knowledge, the most detailed analysis yet of DNA binding by a long zinc finger array, make clear that the binding specificities of PRDM9, and possibly other long array zinc finger proteins, are unusually complex. Genome Biol 2013 Apr 24; 14(4):R3
