Biology subjects

Dang, N.

Publications and source records attributed to Dang, N..

6 recordsLinked to original sources

bioRxiv2025

Deciphering complex interactions between LTR retrotransposons and three Papaver species using LTR_Stream

Long terminal repeat retrotransposons (LTR-RTs), a major type of class I transposable elements (TEs), are the most abundant repeat element in plants. The study of the interactions between LTR-RTs and the host genome relies on high-resolution characterization of LTR-RTs. However, for non-model species, this remains a challenge. To address this, we developed LTR_Stream for sub-lineage clustering of LTR-RTs in specific or closely related species, providing higher precision than current database-based lineage-level clustering. Using LTR_Stream, we analyzed Retand LTR-RTs in three Papaver species. Our findings show that high-resolution clustering reveals complex interactions between LTR-RTs and the host genome. For instance, we found autonomous Retand elements could spread among the ancestors of different subgenomes, like retroviruses pandemics, enriching genetic diversity. Additionally, we identified that specific truncated fragments containing transcription factors motifs such as TCP and bZIP may contribute to generation of novel TAD-like boundaries. Notably, our pre- and post-allopolyploidization comparisons show that these effects diminished after allopolyploidization, suggesting that allopolyploidization may be one of the mechanisms by which Papaver species cope with LTR-RTs. We demonstrated the potential application of LTR_Stream and provided a reference case for studying the interactions between LTR-RTs and the host genome in non-model plant species.

bioinformatics↗

bioRxiv2024

Senataxin and DNA-PKcs Redundantly Promote Non-Homologous End Joining Repair of DNA Double Strand Breaks During V(D)J Recombination

Non-homologous end joining (NHEJ) is required for repairing DNA double strand breaks (DSBs) generated by the RAG endonuclease during lymphocyte antigen receptor gene assembly by V(D)J recombination. The Ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) kinases regulate functionally redundant pathways required for NHEJ. Here we report that loss of the senataxin helicase leads to a significant defect in RAG DSB repair upon inactivation of DNA-PKcs. The NHEJ function of senataxin is redundant with the RECQL5 helicase and the HLTF translocase and is epistatic with ATM. Co-inactivation of ATM, RECQL5 and HLTF results in an NHEJ defect similar to that from the combined deficiency of DNA-PKcs and senataxin or losing senataxin, RECQL5 and HLTF. These data suggest that ATM and DNA-PKcs regulate the functions of senataxin and RECQL5/HLTF, respectively to provide redundant support for NHEJ.

cell biology↗

bioRxiv2024

Near telomere-to-telomere genome assemblies of two Chlorella species unveil the composition and evolution of centromeres in green algae

BackgroundCentromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. ResultsWe constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. ConclusionsThis study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.

genomics↗

bioRxiv2022

Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet

As the state-of-the-art sequencing technologies and computational methods enable investigation of challenging regions in the human genome, an update variant benchmark is demanded. Herein, we sequenced a Chinese Quartet, consisting of two monozygotic twin daughters and their biological parents, with multiple advanced sequencing platforms, including Illumina, BGI, PacBio, and Oxford Nanopore Technology. We phased the long reads of the monozygotic twin daughters into paternal and maternal haplotypes using the parent-child genetic map. For each haplotype, we utilized advanced long reads to generate haplotype-resolved assemblies (HRAs) with high accuracy, completeness, and continuity. Based on the ingenious quartet samples, novel computational methods, high-quality sequencing reads, and HRAs, we established a comprehensive variant benchmark, including 3,883,283 SNVs, 859,256 Indels, 9,678 large deletions, 15,324 large insertions, 40 inversions, and 31 complex structural variants shared between the monozygotic twin daughters. In particular, the preciously excluded regions, such as repeat regions and the human leukocyte antigen (HLA) region, were systematically examined. Finally, we illustrated how the sequencing depth correlated with the de novo assembly and variant detection, from which we learned that 30 x HiFi is a balance between performance and cost. In summary, this study provides high-quality haplotype-resolved assemblies and a variant benchmark for two Chinese monozygotic twin samples. The benchmark expanded the regions of the previous report and adapted to the evolving sequencing technologies and computational methods.

genomics↗

bioRxiv2021

Liver-specific Deletion Of Small Heterodimer Partner Alters Enterohepatic Bile Acid Levels And Promotes Bile Acid-Mediated Proliferation In Male Mice.

Small heterodimer partner (Shp) regulates several metabolic processes, including bile acid levels, but lacks the conserved DNA binding domain. Phylogenetic analysis revealed conserved genetic evolution of Shp, Fxr, Cyp7a1 and Cyp27a1, underscoring the importance of these molecules in maintaining bile acid homeostasis. Shp, although primarily studied as a downstream target of Farnesoid X Receptor (Fxr), has a distinct hepatic role that is poorly understood. Here we report that liver-specific Shp knockout (LShpKO) mice have impaired negative feedback of Cyp7a1 and Cyp8b1 upon bile acid challenge and demonstrate that a single copy of the Shp gene is sufficient to maintain this response. LShpKO mice also exhibit elevated total bile acid pool with higher bile acid fraction in the intestine mimicking the 1% cholic acid (CA) fed control mice. Agonistic activation of Fxr (GW4064) in the LShpKO did not alter the elevated basal expression of Cyp8b1 but lowered Cyp7a1 expression. We found that deletion of Shp led to an enrichment of distinct motifs and pathways associated with circadian rhythm, amino and carboxylic acid metabolism, copper ion transport, and DNA synthesis. LShpKO livers displayed a higher basal proliferation that was exacerbated specifically with bile acid challenge but not with another liver mitogen, TCPOBOP (TC). Overall, our data indicate that hepatic SHP uniquely regulates certain proliferative and metabolic cues.

physiology↗

bioRxiv2020

Endogenous SIRT3 activity is dispensable for normal hearing recovery after noise exposure in young adult mice

Occupational noise-induced hearing loss (NIHL) affects millions of people worldwide and presents a large social and personal burden. Some genetic variants in the mitochondrial oxidative stress response correlate strongly with susceptibility to NIHL in both humans and mice. Here we test the hypothesis that SIRT3, a regulator of the mitochondrial oxidative stress response, is required in mice for endogenous recovery of auditory thresholds after a sub-traumatic noise exposure. We expose homozygous Sirt3-KO mice and their wild-type littermates to a noise dose that confers a temporary threshold shift, but is not sufficient to permanently reduce cochlear function, compromise cell survival, or damage synaptic structures. We find no difference in hearing function after recovery from noise exposure between the two genotypes, when measured by either auditory brainstem response (ABR) or distortion product otoacoustic emissions (DPOAE). We show that SIRT3-specific immunoreactivity is present in outer hair cells, around the post-synaptic regions of inner hair cells, and faintly within inner hair cells. Nonetheless, outer hair cells and auditory synapses show no increase in loss after noise exposure in the homozygous Sirt3-KO mouse. These data show that SIRT3-dependent processes are not necessary for endogenous hearing recovery after a single, sub-traumatic noise exposure. They demonstrate the existence of cellular mechanisms of cochlear homeostasis in addition to the mitochondrial oxidative stress response. We also present a novel statistical analysis for identifying differences between peak 1 amplitude progressions in ABR waveforms.

neuroscience↗