Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Cross, George A M
Type of Medium
Language
Year
  • 1
    Language: English
    In: Biochemical and Biophysical Research Communications, 2008, Vol.368(4), pp.846-851
    Description: Some inroads have been made into characterizing histone variants and post translational modifications of histones in . Histone variant H2BV lysine 129 is homologous to H2B lysine 123, whose ubiquitination is required for methylation of H3 lysines 4 and 79. We show that H2BV K129 is not ubiquitinated, but trimethylation of H3 K4 and K76, homologs of H3 K4 and K79 in yeast, was enriched in nucleosomes containing H2BV. Mutation of H2BV K129 to alanine or arginine did not disrupt H3 K4 or K76 methylation. These data suggest that H3 K4 and K76 methylation in trypanosomes is regulated by a novel mechanism, possibly involving the replacement of H2B with H2BV in the nucleosome.
    Keywords: Chromatin Structure ; Histone Methylation ; Histone Modification ; Histone Ubiquitination ; Histone Variant ; Mass Spectrometry ; Nucleosome ; Trypanosoma Brucei ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 08 May 2007, Vol.104(19), pp.7821-6
    Description: Adenosine-to-inosine editing in the anticodon of tRNAs is essential for viability. Enzymes mediating tRNA adenosine deamination in bacteria and yeast contain cytidine deaminase-conserved motifs, suggesting an evolutionary link between the two reactions. In trypanosomatids, tRNAs undergo both cytidine-to-uridine and adenosine-to-inosine editing, but the relationship between the two reactions is unclear. Here we show that down-regulation of the Trypanosoma brucei tRNA-editing enzyme by RNAi leads to a reduction in both C-to-U and A-to-I editing of tRNA in vivo. Surprisingly, in vitro, this enzyme can mediate A-to-I editing of tRNA and C-to-U deamination of ssDNA but not both in either substrate. The ability to use both DNA and RNA provides a model for a multispecificity editing enzyme. Notably, the ability of a single enzyme to perform two different deamination reactions also suggests that this enzyme still maintains specificities that would have been found in the ancestor deaminase, providing a first line of evidence for the evolution of editing deaminases.
    Keywords: RNA Editing ; Adenosine Deaminase -- Physiology ; Cytidine Deaminase -- Physiology
    ISSN: 0027-8424
    E-ISSN: 10916490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: FEBS Letters, 2006, Vol.580(9), pp.2306-2310
    Description: To start to understand the role of chromatin structure in regulating transcription in trypanosomes, we analyzed covalent modifications on the four core histones of . We found unusually few modifications in the N-terminal tails, which are abundantly modified in other organisms and whose sequences, but not composition, are highly divergent in trypanosomes. In contrast, the C-terminal region of H2A appears to be hyper-acetylated. Surprisingly, the N-terminal alanines of H2A, H2B, and H4, were mono-methylated, a modification that has not been described previously for histones. Possible functions and evolutionary explanations for these unusual histone modifications are discussed.
    Keywords: Histone Methylation ; Histone Acetylation ; Histone Modification ; Mass Spectrometry ; Edman ; Trypanosoma Brucei ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Molecular Microbiology, February 2008, Vol.67(4), pp.762-771
    Description: Post‐translational histone modifications have been studied intensively in several eukaryotes. It has been proposed that these modifications constitute a ‘histone code’ that specifies epigenetic information for transcription regulation. With a limited number of histone‐modifying enzymes, implying less redundancy, represents an excellent system in which to investigate the function of individual histone modifications and histone‐modifying enzymes. In this study, we characterized the acetylation of lysine 4 of histone H4 (H4K4), the most abundant acetylation site in histones. Because of the large sequence divergence of histones, we generated highly specific antibodies to acetylated and unmodified H4K4. Immunofluorescence microscopy and Western blots with sorted cells revealed a strong enrichment of unmodified H4K4 in S phase and suggested a G1/G0‐specific masking of the site, owing to non‐covalently binding factors. Finally, we showed that histone acetyltransferase 3 (HAT3) is responsible for H4K4 acetylation and that treatment of cells with the protein synthesis inhibitor cycloheximide led to an almost instantaneous loss of unmodified H4K4 sites. As HAT3 is located inside the nucleus, our findings suggest that newly synthesized histone H4 with an unmodified K4 is imported rapidly into the nucleus, where it is acetylated, possibly irreversibly.
    Keywords: Acetates ; Protein Synthesis ; Histones;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Nature Reviews Microbiology, 2009, Vol.7(7), p.504
    Description: Epigenetic regulation is important in many facets of eukaryotic biology. Recent work has suggested that the basic mechanisms underlying epigenetic regulation extend to eukaryotic parasites. The identification of post-translational histone modifications and chromatin-modifying enzymes is beginning to reveal both common and novel functions for chromatin in these parasites. In this Review, we compare the role of epigenetics in African trypanosomes and humans in several biological processes. We discuss how the study of trypanosome chromatin might help us to better understand the evolution of epigenetic processes.
    Keywords: Parasites ; Histones ; Post-Translation ; Chromatin ; Epigenetics ; Enzymes ; Evolution ; Trypanosoma ; Genetics & Taxonomy ; DNA Metabolism & Structure;
    ISSN: 1740-1526
    E-ISSN: 17401534
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Molecular Cell, 2006, Vol.23(4), pp.497-507
    Description: DOT1 is an evolutionarily conserved histone H3 lysine 79 (H3K79) methyltransferase. K79 methylation is associated with transcriptional activation, meiotic checkpoint control, and DNA double-strand break (DSB) responses. has two homologs, DOT1A and DOT1B, which are responsible for dimethylation and trimethylation of H3K76, respectively (K76 in is synonymous to K79 in other organisms). K76 dimethylation is only detectable during mitosis, whereas trimethylation occurs throughout the cell cycle. Deletion of DOT1B resulted in dimethylation of K76 throughout the cell cycle and caused subtle defects in cell cycle regulation and impaired differentiation. RNAi-mediated depletion of DOT1A appears to disrupt a mitotic checkpoint, resulting in premature progression through mitosis without DNA replication, generating a high proportion of cells with a haploid DNA content, an unprecedented state for trypanosomes. We propose that DOT1A and DOT1B influence the trypanosome cell cycle by regulating the degree of H3K76 methylation.
    Keywords: Microbio ; DNA ; Biology
    ISSN: 1097-2765
    E-ISSN: 1097-4164
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Molecular & Biochemical Parasitology, 2006, Vol.149(1), pp.102-107
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.molbiopara.2006.04.005 Byline: Christian J. Janzen (a), Frederick van Deursen (b), Huafang Shi (c), George A.M. Cross (a), Keith R. Matthews (b), Elisabetta Ullu (c)(d) Keywords: Trypanosomes; RNA interference; TbAGO1; VSG; Life-cycle Author Affiliation: (a) Laboratory of Molecular Parasitology, The Rockefeller University, Box 185, 1230 York Avenue, New York, NY 10021-6399, USA (b) Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK (c) Department of Internal Medicine, Yale Medical School, BCMM 136D, 295 Congress Avenue, Box 9812, New Haven, CT, 06536-8012, USA (d) Department of Cell Biology, Yale Medical School, BCMM 136D, 295 Congress Avenue, Box 9812, New Haven, CT, 06536-8012, USA Article History: Received 26 February 2006; Revised 1 April 2006; Accepted 7 April 2006
    Keywords: Trypanosomes ; RNA Interference ; Tbago1 ; Vsg ; Life-Cycle ; Biology ; Chemistry ; Zoology
    ISSN: 0166-6851
    E-ISSN: 1872-9428
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Molecular & Biochemical Parasitology, 2007, Vol.156(1), pp.41-50
    Description: Several biological processes in are affected by chromatin structure, including gene expression, cell cycle regulation, and life-cycle stage differentiation. In and other organisms, chromatin structure is dependent upon posttranslational modifications of histones, which have been mapped in detail. The tails of the four core histones of are highly diverged from those of mammals and yeasts, so sites of potential modification cannot be reliably inferred, and no cross-species antibodies are available to map the modifications. We therefore undertook an extensive survey to identify posttranslational modifications by Edman degradation and mass spectrometry. Edman analysis showed that the N-terminal alanine of H2A, H2B, and H4 could be monomethylated. We found that the histone H4 N-terminus is heavily modified, while, in contrast to other organisms, the histone H2A and H2B N-termini have relatively few modifications. Histone H3 appears to have a number of modifications at the N-terminus, but we were unable to assign many of these to a specific amino acid. Therefore, we focused our efforts on uncovering modification states of H4. We discuss the potential relevance of these modifications.
    Keywords: Trypanosoma Brucei ; Histone Acetylation ; Histone Methylation ; Transcription ; Nucleosome ; Chromatin ; Biology ; Chemistry ; Zoology
    ISSN: 0166-6851
    E-ISSN: 1872-9428
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: PLoS Biology, 2008, Vol.6(7), p.e161
    Description: To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type of VSG at the cell surface and periodically and very rapidly switching the expressed VSG. Transcriptional switching between resident telomeric VSG genes does not involve DNA rearrangements, and regulation is probably epigenetic. The histone methyltransferase DOT1B is a nonessential protein that trimethylates lysine 76 of histone H3 in Trypanosoma brucei . Here we report that transcriptionally silent telomeric VSG s become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected. DOT1B also is involved in the kinetics of VSG switching: in ΔDOT1B cells, the transcriptional switch is so slow that cells expressing two VSGs persist for several weeks, indicating that monoallelic transcription is compromised. We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei . ; The surface of , a unicellular parasite that lives in the bloodstream of its mammalian host, is coated with glycoprotein (VSG) molecules. To evade elimination by the immune system, this parasite replaces its coat with one tailored from another glycoprotein variant. Even though there are hundreds of genes in the genome, this process, called antigenic variation, works because all are silenced except for the one that encodes the current coat. In this work, we show that the chromatin-modifying enzyme DOT1B helps to epigenetically regulate the number of VSGs each parasite can have at a time at the surface and how fast each parasite can switch from one coat to another. In parasites lacking DOT1B, silent genes become partially active and the switch from one VSG to another slows down, allowing two different VSGs to appear on the surface of an individual parasite at the same time. Our studies reveal the importance of epigenetics in regulating genes and provide new insights toward the understanding of this unique survival device. ; Antigenic variation in relies on monoallelic expression of a multigene family. New evidence shows that a chromatin-modifying enzyme prevents simultaneous expression of different proteins at the parasite's surface.
    Keywords: Research Article ; Cell Biology ; Genetics And Genomics ; Infectious Diseases ; Microbiology ; Molecular Biology
    ISSN: 1544-9173
    E-ISSN: 1545-7885
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Nucleic acids research, 2004, Vol.32(22), pp.6575-84
    Description: KU is a heterodimer, consisting of approximately 70 and approximately 80 kDa subunits (KU70 and KU80, respectively), which is involved in a variety of nuclear functions. We generated tbKU80-deficient trypanosomes to explore the potential role of the tbKU complex in telomere maintenance and transcriptional regulation of variant surface glycoprotein (VSG) genes in Trypanosoma brucei. Using real-time PCR, we demonstrated that the expression of several different VSG genes remains tightly regulated in tbKU80-deficient bloodstream-form cell lines, suggesting that VSG transcription profiles do not change in these cells. Owing to developmental silencing of the VSG Expression Sites (ES), no VSG is transcribed in the insect procyclic stage. With a green fluorescent protein reporter system, we showed that tbKU80-deficient mutants are fully capable of ES silencing after differentiation into procyclic forms. Using T7 RNA polymerase to explore the transcriptional accessibility of ES chromatin in vivo, we demonstrated that tbKU80-deficient bloodstream-form cells were able to generate transcriptionally repressed ES chromatin after differentiation into procyclic cells. Finally, we demonstrated progressive telomere shortening in tbKU80-deficient mutants. The possible function of tbKU80 in telomere maintenance and regulation of telomerase is discussed.
    Keywords: Gene Silencing ; Antigens, Nuclear -- Physiology ; DNA-Binding Proteins -- Physiology ; Telomere -- Metabolism ; Trypanosoma Brucei Brucei -- Genetics
    E-ISSN: 1362-4962
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages