TY  - JOUR
A1  - Reynolds, David L.
A1  - Hofmeister, Brigitte T.
A1  - Cliffe, Laura
A1  - Siegel, T. Nicolai
A1  - Andersson, Britta A.
A1  - Beverley, Stephen M.
A1  - Schmitz, Robert J.
A1  - Sabatini, Robert
T1  - Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination
JF  - Molecular Microbiology
N2  - The genomes of kinetoplastids are organized into polycistronic gene clusters that are flanked by the modified DNA base J. Previous work has established a role of base J in promoting RNA polymerase II termination in Leishmania spp. where the loss of J leads to termination defects and transcription into adjacent gene clusters. It remains unclear whether these termination defects affect gene expression and whether read through transcription is detrimental to cell growth, thus explaining the essential nature of J. We now demonstrate that reduction of base J at specific sites within polycistronic gene clusters in L. major leads to read through transcription and increased expression of downstream genes in the cluster. Interestingly, subsequent transcription into the opposing polycistronic gene cluster does not lead to downregulation of sense mRNAs. These findings indicate a conserved role for J regulating transcription termination and expression of genes within polycistronic gene clusters in trypanosomatids. In contrast to the expectations often attributed to opposing transcription, the essential nature of J in Leishmania spp. is related to its role in gene repression rather than preventing transcriptional interference resulting from read through and dual strand transcription.
KW  - Trypanosoma-brucei
KW  - Transcription initiation
KW  - Messenger RNA
KW  - DNA
KW  - Genome
KW  - Cruzi
KW  - Hydroxymethyluracil
KW  - Expression
KW  - Parasite
KW  - Glucosyltransferase
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187727
VL  - 101
IS  - 4
ER  - 
TY  - JOUR
A1  - Schneider, Eberhard
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - El Hajj, Nady
A1  - Haaf, Thomas
T1  - CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development
JF  - Gene
N2  - Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny.
KW  - Autism spectrum disorders
KW  - DNA methylation
KW  - Genome
KW  - Autism
KW  - Frontal cortex
KW  - Human prefrontal cortex
KW  - Gene-expression
KW  - Schizophrenia
KW  - Patterns
KW  - Transcription
KW  - Epigenetics
KW  - Environment
KW  - Fetal brain development
KW  - DNA methylation dynamics
KW  - Methylome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186936
VL  - 592
IS  - 1
ER  -