Search bioRxivSearch

Biology subjects

Vogel, T.

Publications and source records attributed to Vogel, T..

2 recordsLinked to original sources

Snow Microbiome Functional Analyses Reveal Novel Microbial Metabolism of Complex Organic Compounds

Microbes active in extremely cold environments are not as well explored as those of other extreme environments. Studies have revealed a substantial microbial diversity and identified cold-specific microbiome molecular functions. We analyzed the metagenomes and metatranscriptomes of twenty snow samples collected during early and late spring in Svalbard, Norway using our computational read-based microbiome function annotation tool, mi-faser. Our results revealed a more diverse microbiome functional capacity and activity in the early compared to in the late spring samples. The dissimilarity between the metagenomes and metatranscriptomes of the same samples was also significantly higher in the early spring. These findings suggest that early spring samples may contain a larger fraction of DNA of dormant organisms, while late spring samples reflect a new community that is metabolically active. We additionally showed that the abundance of the sequencing reads mapping to the fatty acid synthesis-related microbial pathways was significantly positively correlated with organic acid levels, in both our late spring metagenomes and metatranscriptomes. Moreover, the geraniol degradation pathway and the styrene degradation pathway read abundances correlated and inversely correlated, respectively, with the organic acid levels. These results suggest a possible nutrient switch. Our study thus highlights the activity of microbial degradation pathways of complex organic compounds previously unreported at low temperatures.

bioinformatics

DOT1L Methyltransferase Activity Preserves SOX2-Enhancer Accessibility And Prevents Activation of Repressed Genes In Murine Stem Cells

BackgroundDuring cellular differentiation, the chromatin landscape changes dynamically and contributes to the activation of cell-type specific transcriptional programs. Disruptor of telomeric silencing 1-like (DOT1L) is a histone methyltransferase that mediates mono-, di- and trimethylation of lysine 79 of histone H3 (H3K79me1, 2, 3). Its enzymatic activity is critical for driving cellular differentiation into cardiomyocytes, chondrocytes and neurons, from embryonic or other type of stem cells in physiological settings. Ectopic localization of DOT1L in MLL-rearranged leukemias is causative for leukemogenesis and relapse. Little is known about the causal relevance of DOT1L methyltransferase activity in the global chromatin context and how its enzymatic function affects transcriptional and global chromatin states. Recent reports conducted in leukemia cell models have suggested that deposition of H3K79me2 may be critical to preserve histone H3K27 acetylation (ac) and enhancer activity, and to sustain expression of highly transcribed genes. If and to what extent DOT1L affects chromatin states and enhancer activity during physiological differentiation processes is currently unknown. ResultsWe measure global changes of seven histone modifications during the differentiation process via high-throughput and quantitative ChIP-seq in an in-vitro neuronal differentiation model of mouse embryonic stem cells (mESC). We observe that H3K27ac globally decreases, whereas H3K79me2 globally increases during differentiation, while other modifications remain globally unaltered. Pharmacological inhibition of DOT1L in mESC and mESC-derived neural progenitors results in decreased expression of highly transcribed genes and increased expression of normally repressed genes. Acute DOT1L inhibition primes neural progenitors towards a mature differentiation state. Transcriptional downregulation associates with decreased accessibility of enhancers specifically bound by the master regulator SOX2. ConclusionsIn-vitro neuronal differentiation couples with a genome-wide accumulation of H3K79me2, never described previously in mammalian cells. Acute inhibition of DOT1L is sufficient to initiate a defined transcriptional program, which biases the transcriptome of neural progenitor cells towards neuronal differentiation. H3K79me2 is not generally causative for maintaining transcriptional levels at a genome-wide scale. In contrast, DOT1L inactivation reduces the chromatin accessibility of enhancers bound by SOX2 in-vivo, thereby reducing the expression level of a restricted number of genes. Our work establishes that DOT1L activity gates differentiation of progenitors by allowing SOX2-dependent transcription of stemness programs.

genomics