Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei

Please always quote using this URN: urn:nbn:de:bvb:20-opus-117863
  • Base J, beta-d-glucosyl-hydroxymethyluracil, is an epigenetic modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. J is enriched at sites involved in RNA polymerase ( RNAP) II initiation and termination. Reduction of J in Leishmania tarentolae via growth in BrdU resulted in cell death and indicated a role of J in the regulation of RNAP II termination. To further explore J function in RNAP II termination among kinetoplastids and avoid indirect effects associated with BrdU toxicity and genetic deletions,Base J, beta-d-glucosyl-hydroxymethyluracil, is an epigenetic modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. J is enriched at sites involved in RNA polymerase ( RNAP) II initiation and termination. Reduction of J in Leishmania tarentolae via growth in BrdU resulted in cell death and indicated a role of J in the regulation of RNAP II termination. To further explore J function in RNAP II termination among kinetoplastids and avoid indirect effects associated with BrdU toxicity and genetic deletions, we inhibited J synthesis in Leishmania major and Trypanosoma brucei using DMOG. Reduction of J in L. major resulted in genome-wide defects in transcription termination at the end of polycistronic gene clusters and the generation of antisense RNAs, without cell death. In contrast, loss of J in T. brucei did not lead to genome-wide termination defects; however, the loss of J at specific sites within polycistronic gene clusters led to altered transcription termination and increased expression of downstream genes. Thus, J regulation of RNAP II transcription termination genome-wide is restricted to Leishmania spp., while in T. brucei it regulates termination and gene expression at specific sites within polycistronic gene clusters.show moreshow less

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Metadaten
Author: David Reynolds, Laura Cliffe, Dr. Konrad U. FörstnerORCiDGND, Chung-Chau Hon, T. Nicolai Siegel, Robert Sabatini
URN:urn:nbn:de:bvb:20-opus-117863
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):Nucleic Acids Research
Year of Completion:2014
Volume:42
Issue:15
Pagenumber:9717-9729
Source:Nucleic Acids Research, 2014, Vol. 42, No. 15, 9717–9729. doi:10.1093/nar/gku714
DOI:https://doi.org/10.1093/nar/gku714
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25104019
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:5-bromodeoxyuridine; DNA glycosation; RNA-polymerase-II; SWI2/SNF2-like protein; gene expression; genome; hela cells; messenger RNA; polycistronic transcription; variant surface glycoprotein
Release Date:2015/08/29
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung