Faculty Opinions recommendation of Genome-wide analyses of light-regulated genes in Aspergillus nidulans reveal a complex interplay between different photoreceptors and novel photoreceptor functions.

SummaryThe Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the region’s population history. Here we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher Eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

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Genome Wide Analysis Reveals the Role of VadA in Stress Response, Germination, and Sterigmatocystin Production in Aspergillus nidulans Conidia

Microorganisms ◽

10.3390/microorganisms8091319 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1319 ◽

Cited By ~ 1

Author(s):

Ye-Eun Son ◽

Hee-Soo Park

Keyword(s):

Stress Response ◽

Secondary Metabolism ◽

Aspergillus Nidulans ◽

Gene Clusters ◽

Tube Formation ◽

Spore Viability ◽

Genetic Changes ◽

Genome Wide ◽

Trehalose Biosynthesis

In the Aspergillus species, conidia are asexual spores that are infectious particles responsible for propagation. Conidia contain various mycotoxins that can have detrimental effects in humans. Previous study demonstrated that VadA is required for fungal development and spore viability in the model fungus Aspergillus nidulans. In the present study, vadA transcriptomic analysis revealed that VadA affects the mRNA expression of a variety of genes in A. nidulans conidia. The genes that were primarily affected in conidia were associated with trehalose biosynthesis, cell-wall integrity, stress response, and secondary metabolism. Genetic changes caused by deletion of vadA were related to phenotypes of the vadA deletion mutant conidia. The deletion of vadA resulted in increased conidial sensitivity against ultraviolet stress and induced germ tube formation in the presence and absence of glucose. In addition, most genes in the secondary metabolism gene clusters of sterigmatocystin, asperfuranone, monodictyphenone, and asperthecin were upregulated in the mutant conidia with vadA deletion. The deletion of vadA led to an increase in the amount of sterigmatocystin in the conidia, suggesting that VadA is essential for the repression of sterigmatocystin production in conidia. These results suggest that VadA coordinates conidia maturation, stress response, and secondary metabolism in A. nidulans conidia.

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A novel fungal gene regulation system based on inducible VPR-dCas9 and nucleosome map-guided sgRNA positioning

Applied Microbiology and Biotechnology ◽

10.1007/s00253-020-10900-9 ◽

2020 ◽

Vol 104 (22) ◽

pp. 9801-9822

Author(s):

Andreas Schüller ◽

Lisa Wolansky ◽

Harald Berger ◽

Lena Studt ◽

Agnieszka Gacek-Matthews ◽

...

Keyword(s):

Aspergillus Nidulans ◽

Target Genes ◽

Negative Impact ◽

Constitutive Expression ◽

Gene Clusters ◽

Regulation System ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Genome Wide ◽

A Genome

Abstract Programmable transcriptional regulation is a powerful tool to study gene functions. Current methods to selectively regulate target genes are mainly based on promoter exchange or on overexpressing transcriptional activators. To expand the discovery toolbox, we designed a dCas9-based RNA-guided synthetic transcription activation system for Aspergillus nidulans that uses enzymatically disabled “dead” Cas9 fused to three consecutive activation domains (VPR-dCas9). The dCas9-encoding gene is under the control of an estrogen-responsive promoter to allow induction timing and to avoid possible negative effects by strong constitutive expression of the highly active VPR domains. Especially in silent genomic regions, facultative heterochromatin and strictly positioned nucleosomes can constitute a relevant obstacle to the transcriptional machinery. To avoid this negative impact and to facilitate optimal positioning of RNA-guided VPR-dCas9 to targeted promoters, we have created a genome-wide nucleosome map from actively growing cells and stationary cultures to identify the cognate nucleosome-free regions (NFRs). Based on these maps, different single-guide RNAs (sgRNAs) were designed and tested for their targeting and activation potential. Our results demonstrate that the system can be used to regulate several genes in parallel and, depending on the VPR-dCas9 positioning, expression can be pushed to very high levels. We have used the system to turn on individual genes within two different biosynthetic gene clusters (BGCs) which are silent under normal growth conditions. This method also opens opportunities to stepwise activate individual genes in a cluster to decipher the correlated biosynthetic pathway. Keypoints • An inducible RNA-guided transcriptional regulator based on VPR-dCas9 was established in Aspergillus nidulans. • Genome-wide nucleosome positioning maps were created that facilitate sgRNA positioning. • The system was successfully applied to activate genes within two silent biosynthetic gene clusters.

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Comparison of gene expression signatures of diamide, H2O2 and menadione exposed Aspergillus nidulans cultures – linking genome-wide transcriptional changes to cellular physiology

BMC Genomics ◽

10.1186/1471-2164-6-182 ◽

2005 ◽

Vol 6 (1) ◽

Cited By ~ 52

Author(s):

István Pócsi ◽

Márton Miskei ◽

Zsolt Karányi ◽

Tamás Emri ◽

Patricia Ayoubi ◽

...

Keyword(s):

Gene Expression ◽

Aspergillus Nidulans ◽

Cellular Physiology ◽

Genome Wide ◽

Gene Expression Signatures ◽

Transcriptional Changes

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Genetic background of atherosclerosis and its risk factors

10.1093/med/9780199656653.003.0002 ◽

2015 ◽

Author(s):

Lesca M. Holdt ◽

Daniel Teupser

Keyword(s):

Risk Factors ◽

Association Studies ◽

Effect Sizes ◽

Genome Wide Association Studies ◽

Therapeutic Approaches ◽

Complex Interplay ◽

Risk Variants ◽

Genome Wide ◽

Atherosclerosis Risk ◽

Genetically Determined

This chapter is concerned with how atherosclerosis risk is modulated by a complex interplay between genetic and environmental risk factors. The contribution of genetics to the variability of atherosclerosis risk is estimated as 50%. Recent genome-wide association studies have led to the identification of over 50 gene variants which modulate atherogenesis. Risk factors for atherosclerosis are also partly genetically determined and some of the variants which play a role in atherogenesis overlap with those modulating its risk factors. However, the current relevance of these findings for clinical practice is limited, mainly due to the small effect sizes of identified risk variants with insufficient discriminatory power, and a large portion of the genetic contribution to atherosclerosis is still unknown. The major promise therefore lies in understanding the pathophysiology of newly identified genes with the perspective of novel therapeutic approaches.

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