Biology subjects

Zhuo, X.

Publications and source records attributed to Zhuo, X..

21 records · Page 2Linked to original sources

bioRxiv2021

Histone acetyltransferases and deacetylases are required for virulence, conidiation, DNA damage repair, and multiple stresses resistance of Alternaria alternata

Histone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5, RTT109, Elp3, Sas3, Sas2, Nat3) and 6 histone deacetylases (HDACs) (Hos2, Rpd3, Hda1, Hos3, Hst2, Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants ({Delta}Gcn5,{Delta} RTT109,{Delta} Elp3,{Delta} Sas3,{Delta} Nat3,{Delta} Hos2, and{Delta} Rpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3, Gcn5, Elp3, RTT109, Hos2), osmotic stress (Sas3, Gcn5, RTT109, Hos2), cell wall-targeting agents (Sas3, Gcn5, Hos2), and fungicide (Gcn5, Hos2).{Delta} Gcn5,{Delta} Sas3 and{Delta} Hos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in{Delta} Gcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover,{Delta} RTT109,{Delta} Gcn5 and{Delta} Hos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in{Delta} Gcn5 and{Delta} Hos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata. ImportanceIn filamentous fungi, HATs and HDACs have been found to be involved in growth, development, virulence, synthesis of secondary metabolites and multi-stress resistance. However, the role of all HATs and HDACs in the same fungal pathogen has not been systematically explored. Our study revealed that HATs and HDACs are required for the vegetative growth, conidiation, pathogenicity, multiple stresses resistance, DNA damage repair, and carbon source utilization in A. alternata. Moreover, HATs and HDACs identified in A. alternata are highly conserved in many notorious pathogenic fungi, such as Magnaporthe grisea and Candida albicans. Therefore, this study not only systematically reveals the biological functions of twelve histone acetylation-required enzymes for the first time, but also provides a foundation for future investigations in A. alternata or other pathogenic fungi.

microbiology↗

bioRxiv2020

Exploring the coronavirus epidemic using the new WashU Virus Genome Browser

Since its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBIs GenBank [1], providing insight into the viruss evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed at https://virusgateway.wustl.edu, and documentation is available at https://virusgateway.readthedocs.io/.

genomics↗

bioRxiv2018

Co-opted transposons help perpetuate conserved higher-order chromosomal structures

Transposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include architectural proteins--such as CTCF, RAD21 and SMC3--that are involved in tethering chromatin loops and marking domain boundaries. The 3D organization of the mammalian genome is intimately linked to its function and is remarkably conserved. However, the mechanisms by which these structural intricacies emerge and evolve have not been thoroughly probed. Here we show that TEs contribute extensively to both the formation of species-specific loops in humans and mice via deposition of novel anchoring motifs, as well as to the maintenance of conserved loops across both species via CTCF binding site turnover. The latter function demonstrates the ability of TEs to contribute to genome plasticity and reinforce conserved genome architecture as redundant loop anchors. Deleting such candidate TEs in human cells leads to a collapse of such conserved loop and domain structures. These TEs are also marked by reduced DNA methylation and bear mutational signatures of hypomethylation through evolutionary time. TEs have long been considered a source of genetic innovation; by examining their contribution to genome topology, we show that TEs can contribute to regulatory plasticity by inducing redundancy and potentiating genetic drift locally while conserving genome architecture globally, revealing a paradigm for defining regulatory conservation in the noncoding genome beyond classic sequence-level conservation.\n\nOne-sentence summaryCo-option of transposable elements maintains conserved 3D genome structures via CTCF binding site turnover in human and mouse.

genomics↗