TY  - JOUR
A1  - Reynolds, David
A1  - Cliffe, Laura
A1  - Förstner, Konrad U.
A1  - Hon, Chung-Chau
A1  - Siegel, T. Nicolai
A1  - Sabatini, Robert
T1  - Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei
JF  - Nucleic Acids Research
N2  - 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.
KW  - RNA-polymerase-II
KW  - variant surface glycoprotein
KW  - SWI2/SNF2-like protein
KW  - messenger RNA
KW  - polycistronic transcription
KW  - DNA glycosation
KW  - hela cells
KW  - gene expression
KW  - genome
KW  - 5-bromodeoxyuridine
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117863
VL  - 42
IS  - 15
ER  -