Biology subjects

Xue, B.

Publications and source records attributed to Xue, B..

54 records · Page 3Linked to original sources

bioRxiv2021

Converting Muscle-mimetic Biomaterials to Cartilage-like Materials

Load-bearing tissues, such as muscle and cartilage, exhibit mechanical properties that often combine high elasticity, high toughness and fast recovery, despite their different stiffness ([~]100 kPa for muscles and one to several MPa for cartilage).1-7 The advance in protein engineering and protein mechanics has made it possible to engineer protein-based biomaterials to mimic soft load-bearing tissues, such as muscles.8-10 However, it is challenging to engineer protein biomaterials to achieve the mechanical properties exhibited by stiff tissues, such as articular cartilage,6,11 or to develop stiff synthetic extracellular matrices for cartilage stem/progenitor cell differentiation12. By employing physical entanglements13 of protein chains and force-induced protein unfolding,14,15 here we report the engineering of a highly tough and stiff protein hydrogel to mimic articular cartilage. By crosslinking an engineered artificial elastomeric protein from its unfolded state, we introduced chain entanglement into the hydrogel network. Upon renaturation, the entangled protein chain network and forced protein unfolding entailed this single network protein hydrogel with superb mechanical properties in both tensile and compression tests, showing a Youngs modulus of [~]0.7 MPa and toughness of 250 kJ/m3 in tensile testing; and [~]1.7 MPa in compressive modulus and toughness of 3.2 MJ/m3. The energy dissipation in both tensile and compression tests is reversible and the hydrogel can recovery its mechanical properties rapidly. Moreover, this hydrogel can withstand a compression stress of >60 MPa without failure, amongst the highest compressive strength achieved by a hydrogel. These properties are comparable to those of articular cartilage, making this protein hydrogel a novel cartilage-mimetic biomaterial. Our study opened up a new potential avenue towards engineering protein hydrogel-based substitute for articular cartilage, and may also help develop protein biomaterials with superb mechanical properties for applications in soft actuators and robotics.

bioengineering↗

bioRxiv2021

Plant Metabolic Network: A multi-species resource of plant metabolic information

Plant metabolism is a pillar of our ecosystem, food security, and economy. To understand and engineer plant metabolism, we first need a comprehensive and accurate annotation of all metabolic information across plant species. As a step towards this goal, we previously created the Plant Metabolic Network (PMN), an online resource of curated and computationally predicted information about the enzymes, compounds, reactions, and pathways that make up plant metabolism. Here we report PMN 15, which contains genome-scale metabolic pathway databases of 126 algal and plant genomes, ranging from model organisms to crops to medicinal plants, and new tools for analyzing and viewing metabolism information across species and integrating omics data in a metabolic context. We systematically evaluated the quality of the databases, which revealed that our semi-automated validation pipeline dramatically improves the quality. We then compared the metabolic content across the 126 organisms using multiple correspondence analysis and found that Brassicaceae, Poaceae, and Chlorophyta appeared as metabolically distinct groups. To demonstrate the utility of this resource, we used recently published sorghum transcriptomics data to discover previously unreported trends of metabolism underlying drought tolerance. We also used single-cell transcriptomics data from the Arabidopsis root to infer cell-type specific metabolic pathways. This work shows the continued growth and refinement of the PMN resource and demonstrates its wide-ranging utility in integrating metabolism with other areas of plant biology. One-sentence SummaryThe Plant Metabolic Network is a collection of databases containing experimentally-supported and predicted information about plant metabolism spanning many species.

plant biology↗

bioRxiv2021

Identity and compatibility of reference genome resources

Genome analysis relies on reference data like sequences, feature annotations, and aligner indexes. These data can be found in many versions from many sources, making it challenging to identify and assess compatibility among them. For example, how can you determine which indexes are derived from identical raw sequence files, or which annotations share a compatible coordinate system? Here, we describe a novel approach to establish identity and compatibility of reference genome resources. We approach this with three advances: First, we derive unique identifiers for each resource; second, we record parent-child relationships among resources; and third, we describe recursive identifiers that determine identity as well as compatibility of coordinate systems and sequence names. These advances facilitate portability, reproducibility, and re-use of genome reference data. Availabilityhttps://refgenie.databio.org

genomics↗

bioRxiv2021

Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations

ObjectiveThe paraventricular nucleus of hypothalamus (PVN) is an integrative center in the brain orchestrating a wide range of physiological and behavioral responses. While the PVN melanocortin 4 receptor (MC4R) signaling (PVNMC4R+) is undoubtedly involved in feeding regulation, the neuroanatomical organization of PVNMC4R+ pathway and its role in diverse physiological and behavioral regulations have not been fully understood. Here we aimed to better characterize the input-output organization of PVNMC4R+ neurons and further test their potential functional roles beyond feeding. MethodsUsing a combination of viral tools, we performed a comprehensive mapping of PVNMC4R+ circuits and tested the effects of chemogenetic activation of PVNMC4R+ neurons on thermogenesis, cardiovascular control and other behavioral regulations beyond feeding. ResultsWe found that PVNMC4R+ neurons broadly innervate many different brain regions known to be important not only for feeding but also for neuroendocrine and autonomic control of thermogenesis and cardiovascular function, including but not limited to preoptic area, median eminence, parabrachial nucleus, locus coeruleus, nucleus of solitary tract, ventrolateral medulla and thoracic spinal cord. Contrary to broad efferent projections, PVNMC4R+ neurons receive monosynaptic inputs from limited brain regions, including medial preoptic nucleus, arcuate and dorsomedial hypothalamic nuclei, and supraoptic nucleus. Consistent with broad efferent projections, chemogenetic activation of PVNMC4R+ neurons not only suppressed feeding but also led to an apparent increase in heart rate, blood pressure and brown adipose tissue thermogenesis. Strikingly, these physiological changes accompanied an unexpected repetitive bedding-removing behavior followed by hypoactivity and resting-like behavior. ConclusionsOur results clarify the neuroanatomical organization of PVNMC4R+ circuits and shed new light on the roles of PVNMC4R+ pathways in autonomic control of thermogenesis, cardiovascular function and other behavioral regulations.

neuroscience↗

bioRxiv2021

Fatty acid metabolic reprogramming promotes C. elegans development

Acetylcholine signaling has been reported to play essential roles in animal metabolic regulation and disease affected by diets. However, the underlying mechanisms that how diets regulate animal physiology and health are not well understood. Here we found that the acetylcholine receptor gene eat-2 was expressed in most of the pharyngeal muscles, which is in accordance to our previous report that EAT-2 received synaptic signals not only from pharyngeal MC neurons. The expression of fatty acid synthesis genes was significantly increased in both eat-2 and tmc-1 fast-growth mutants on CeMM food environment, compared to the wild-type. Excitingly, dietary fatty acids such as 15-methyl-hexadecanoic acid (C17ISO), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0) supplementation, significantly accelerated wild-type worm development on CeMM, indicating that the fatty acid synthesis reprogramming is an essential strategy for C. elegans to regulate its development and growth on CeMM diet. Furthermore, we found that fatty acid elongase gene elo-6 knock-out significantly attenuated eat-2 mutant fast growth, while overexpression of elo-6 could rescue the eat-2; elo-6 double mutant slow development, which suggested that elo-6 played a major role in the above metabolic remodeling. Taken together, our report indicates that diets regulate neuromuscular circuit and modulate C. elegans development via fatty acid metabolic reprogramming. As most of the key genes and metabolites found in this study are conserved in both invertebrate and vertebrate animals, we believed that our results might provide essential clues to the molecular mechanisms underlying interactions among animal nutrition sensation, metabolism reprogramming and developmental regulation. Significance StatementDiets and nutritional composition affect animal development and human health, however the underlying mechanisms remain elusive. We demonstrate that the acetylcholine receptor gene eat-2 is expressed in most of pharyngeal muscles, and the expression of fatty acid synthesis genes is significantly increased in both eat-2 and tmc-1 fast-growth mutants on the synthetic chemical defined CeMM food environment. Dietary supplementation of several fatty acids significantly speed up animal development. Furthermore, we demonstrate that the fatty acid elongase gene elo-6 knock-out attenuates eat-2 mutant fast growth, and overexpression of wild-type elo-6 promotes the eat-2; elo-6 double mutant slow development. Our findings describe that acetylcholine signaling coordinate nutrition sensation and developmental regulation through fatty acid metabolic remodeling.

genetics↗

bioRxiv2020

MondoA Drives Malignancy in cALL through Enhanced Adaptation to Metabolic Stress

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired anti-metabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is to reprogram gene expression in a metabolism-dependent manner. MondoA (also known as MLXIP), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets we found that MondoA overexpression is associated with a worse survival in pediatric common acute lymphoblastic leukemia (cALL). Using CRISPR/Cas9 and RNA interference approaches, we observed that MondoA depletion reduces transformational capacity of cALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid (TCA) cycle activity. Mechanistically, MondoA senses metabolic stress in cALL cells by restricting oxidative phosphorylation through reduced PDH activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in cALL. Our findings give a novel insight into the function of MondoA in pediatric cALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored. Key PointsMondoA maintains aggressiveness and leukemic burden in common ALL, modulating metabolic stress response.

cancer biology↗

bioRxiv2020

miR-200 deficiency promotes lung cancer metastasis by activating cancer-associated fibroblasts

Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.

cancer biology↗

bioRxiv2020

Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Despite various genetic and epigenetic signatures are found to be related with active origins, it remains elusive how the selection of origins is determined. The classic Rosette model proposes that the origins clustered in a chromatin domain are preferentially and simultaneously fired, but direct imaging evidence has been lacking due to insufficient spatial resolution. Here, we applied dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We found that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase, in contrary to the Rosette model. Intriguingly, while both active and dormant origins are distributed homogeneously in the TAD during the G1 phase, active origins relocate to the TAD periphery before entering the S phase. We proved that such origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observed that the replication machinery protein PCNA forms immobile clusters around the TADs at the G1/S transition, which explains why origins at the TAD periphery are preferentially fired. Thus, we propose a "Chromatin Re-organization Induced Selective Initiation" (CRISI) model that the transcription-coupled chromatin structural re-organization determines the selection of replication origins, which transcends the scope of specific genetic and epigenetic signatures for origin efficiency. Our in situ super-resolution imaging unveiled coordination among DNA replication, transcription, and chromatin organization inside individual TADs, providing new insights into the biological functions of sub-domain chromatin structural dynamics.

genomics↗

bioRxiv2020

Abortive Intussusceptive Angiogenesis Causes Multi-Cavernous Vascular Malformations

Mosaic inactivation of CCM2 in humans causes cerebral cavernous malformations (CCMs) containing adjacent dilated blood-filled multi-cavernous lesions. We used CRISPR-Cas9 mutagenesis to induce mosaic inactivation of zebrafish ccm2 resulting in a novel lethal multi-cavernous lesion in the embryonic caudal venous plexus (CVP) caused by obstruction of blood flow by intraluminal pillars. These pillars mimic those that mediate intussusceptive angiogenesis; however, in contrast to the normal process, the pillars failed to fuse to split the pre-existing vessel in two. Abortive intussusceptive angiogenesis stemmed from mosaic inactivation of ccm2 leading to patchy klf2a over-expression and resultant aberrant flow signaling. Surviving adult fish manifested histologically-typical hemorrhagic CCM. Formation of mammalian CCM requires the flow-regulated transcription factor KLF2; fish CCM and the embryonic CVP lesion failed to form in klf2a null fish indicating a common pathogenesis with the mammalian lesion. These studies describe a zebrafish CCM model and establish a mechanism that can explain the formation of characteristic multi-cavernous lesions.

developmental biology↗

bioRxiv2020

KinPred: A unified approach and resource for human kinase-substrate predictions

Tyrosine and serine/threonine kinases are essential regulators of cell processes and are important targets for human therapies. Unfortunately, very little is known about specific kinase-substrate relationships, making it difficult to infer meaning from dysregulated phosphoproteomic datasets or for researchers to identify possible kinases that regulate specific or novel phosphorylation sites. The last two decades have seen an explosion in algorithms to extrapolate from what little is known into the larger unknown - predicting kinase relationships with site-specific substrates using a variety of approaches that include the sequence-specificity of kinase catalytic domains and various other factors, such as evolutionary relationships, coexpression, and protein-protein interaction networks. Unfortunately, a number of limitations prevent researchers from easily harnessing these resources, such as loss of resource accessibility, limited information in publishing that results in a poor mapping to a human reference, and not being updated to match the growth of the human phosphoproteome. Here, we propose a methodological framework for publishing predictions in a unified way, which entails ensuring predictions have been run on a current reference proteome, mapping the same substrates and kinases across resources to a common reference, filtering for the human phosphoproteome, and providing methods for updating the resource easily in the future. We applied this framework on three currently available resources, published in the last decade, which provide kinase-specific predictions in the human proteome. Using the unified datasets, we then explore the role of study bias, the emergent network properties of these predictive algorithms, and comparisons within and between predictive algorithms. The combination of the code for unification and analysis, as well as the unified predictions are available under the resource we named KinPred. We believe this resource will be useful for a wide range of applications and establishes best practices for long-term usability and sustainability for new and existing predictive algorithms.

molecular biology↗

bioRxiv2020

Epigenetic Interaction between UTX and DNMT1 Regulates Diet-Induced Myogenic Remodeling in Brown Fat

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

physiology↗

bioRxiv2020

Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue

Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a novel fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NTF3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NTF3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NTF3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NTF3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC+/-). Increasing NTF3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC+/- mice or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NTF3 is an important fat-derived neurotrophic factor regulating SNS innervation, energy metabolism and obesity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2020

Establishment of a marine nematode model for animal functional genomics, environmental adaptation and developmental evolution

Nematodes play key roles in marine ecosystem. Although oceans cover 71% of the Earths surface, none of marine model nematode has been reported. Here, we constructed the first inbred line of free-living marine nematode Litoditis marina, sequenced and assembled its genome. Furthermore, we successfully applied CRISPR/Cas9 genome editing in L. marina. Comparative genomics revealed that immunity and oxygen regulation genes are expanded, which is probably central to its sediment adaptation. While L. marina exhibits massive gene contractions in NHRs, chemoreceptors, xenobiotics detoxification and core histones, which could explain the more defined marine environment. Our experiments showed that dozens of H4 genes in Caenorhabditis elegans might contribute to its adaptation to the complex terrestrial environments, while two H4 genes in L. marina are involved in salinity stress adaptation. Additionally, ninety-two conserved genes appear to be positively selected in L. marina, which may underpin its osmotic, neuronal and epigenetic changes in the sea. With short generation time, highly inbred lines, and genomic resources, our report brings L. marina a promising marine animal model, and a unique satellite marine model to the well-known biomedical model nematode C. elegans. This study will underpin ongoing work on animal functional genomics, environmental adaptation and developmental evolution.

genomics↗

bioRxiv2019

Relationship between True Digestibility of dietary Phosphorus and Gastrointestinal Bacteria of Goats

The present research was conducted to evaluate the connection between the true digestibility of Phosphorus (TDP) in diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-eight Nubian goats were chosen and metabolic experiment was conducted to analyze TDP of research animals. Eight goats were grouped into the high digestibility of phosphorus (HP) phenotype, and another 8 were grouped into the low digestibility of phosphorus (LP) phenotype. And from the rumen, abomasum, jejunim, cecum and colon content of the goats, bacterial 16S rRNA gene amplicons were sequenced. In the rumen 239 genera belonging to 23 phyla, in abomasum 319 genera belonging to 30 phyla, in jejunum 248 genera belonging to 36,in colon 248 genera belonging to 25 phyla and in cecum 246 genera belonging to 23 phyla were noticed. In addition, there was a significant correlation between the TDP and the abundance of Ruminococcaceae_UCG-010, Ruminococcus_2, Ruminococcaceae_UCG-014, Selenomonas_1 and Prevotella in the rumen, Lachnospiraceae_ND3007_group, Saccharofermentans, Ruminococcus_1, Ruminococcaceae_UCG-014, Lachnospiraceae_XPB1014_group and Desulfovibrio in the abomasum, Prevotella, Clostridium_sensu_stricto_1, Fibrobacter, Desulfovibrio and Ruminococcus_2 in the jejunum, Ruminococcaceae_UCG-014 in the colon, and Desulfovibrio in the cecum. Present research trial recommended that the community of gastrointestinal microbiota is a factor affecting TDP in goats.

microbiology↗

bioRxiv2019

Effects of active dry yeast on growth performance, rumen fermentation characteristics and slaughter performance in beef cattle

This study aimed to investigate the effects of active dry yeast (ADY) on rumen microbial composition and slaughter performance of beef cattle. Thirty-two finishing beef cattle (simmental crossbred cattle [male] x cattle-yaks [female]), with an average body weight of 110 {+/-} 12.85 kg, were randomly assigned to one of four treatments: the low plane of nutrition group (Control), low plane of nutrition group + ADY 2 g/head/d (ADY2), low plane of nutrition group + ADY 4 g/head/d (ADY4) and high plane of nutrition group (HPN). ADY supplementation increased average daily gain (P<0.001), and the carcass weight of ADY4 group had no significant difference with HPN group (P>0.05). The serum glutamic-pyruvic transaminase activity in control and ADY4 group was higher than HPN group (P=0.001). The neutral detergent fiber (P=0.022) and acid detergent fiber (P=0.043) digestibility in HPN group was greater than control, but no difference was obtained among ADY2, ADY4 and HPN group (P>0.05). The rumen ammonium nitrogen content in control was greater than ADY2 and ADY4 group (P=0.003), and no difference was obtained ADY2, ADY4 and HPN group (P>0.05). The propionic acid content in the rumen in ADY2, ADY4, and HPN group were greater than control group (P<0.001). The simpson (P=0.014) and shannon (P=0.045) indexes in control and HPN group were greater than ADY4 group. At the phylum level, the relative abundance of Firmicutes in the HPN group was higher than ADY4 group (P=0.015). At the genus level, HPN and ADY4 were clustered together, and the relative abundance of Ruminococcaceae UCG-002 in ADY4 group was higher than control and HPN group (P=0.004). In conclusion, supplementation ADY 4 g/head/d shift the rumen microbial composition of beef cattle fed low plane of nutrition to a more similar level with cattle fed with HPN diet, produced comparable carcass weight with HPN diet.

zoology↗

bioRxiv2019

Accelerated diversification correlated with functional traits shapes extant diversity of the early divergent angiosperm family Annonaceae

BackgroundA major goal of phylogenetic systematics is to understand both the patterns of diversification and the processes by which these patterns are formed. Few studies have focused on the ancient, species-rich Magnoliales clade and its diversification pattern. Within Magnoliales, the pantropically distributed Annonaceae are by far the most genus-rich and species-rich family-level clade, with c. 110 genera and c. 2,400 species. We investigated the diversification patterns across Annonaceae and identified traits that show varied associations with diversification rates using a time-calibrated phylogeny of 835 species (34.6% sampling) and 11,211 aligned bases from eight regions of the plastid genome (rbcL, matK, ndhF, psbA-trnH, trnL-F, atpB-rbcL, trnS-G, and ycf1). Two hypotheses that might explain patterns of diversification--the museum model and heterogeneous diversification rates--are also evaluated.\n\nResultsTwelve rate shifts were identified using BAMM: in Annona, Artabotrys, Asimina, Drepananthus, Duguetia, Goniothalamus, Guatteria, Uvaria, Xylopia, the tribes Miliuseae and Malmeeae, and the Desmos-Dasymaschalon-Friesodielsia-Monanthotaxis clade (which collectively account for over 80% of the total species richness in the family). TurboMEDUSA and method-of-moments estimator analyses showed largely congruent results. A positive relationship between species richness and diversification rate is revealed using PGLS. We further explore the possible role of selected traits (habit, pollinator trapping, floral sex expression, pollen dispersal unit, anther septation, and seed dispersal unit) in shaping diversification patterns, based on inferences of BiSSE, MuSSE, HiSSE, and FiSSE analyses. Our results suggest that the liana habit, the presence of circadian pollinator trapping, androdioecy, and the dispersal of seeds as single-seeded monocarp fragments are closely correlated with higher diversification rates; pollen aggregation and anther septation, in contrast, are associated with lower diversification rates.\n\nConclusionOur results show that the high species richness in Annonaceae is likely the result of recent increased diversification rather than the steady accumulation of species via the museum model. BAMM, turboMEDUSA, and the method-of-moments estimator all indicate heterogeneity in diversification rates across the phylogeny, with different traits associated with shifts in diversification rates in different Annonaceae clades.

evolutionary biology↗

bioRxiv2019

Chromatin-lamin B1 interaction promotes genomic compartmentalization and constrains chromatin dynamics

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized chromatin architecture and dynamics remains poorly understood. Here by combining imaging and Hi-C sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, the inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). We further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nuclear interior. Taken together, our data suggest that chromatin-lamin B1 interactions promote chromosomal territory segregation and genomic compartmentalization, and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and dynamics.

genomics↗

bioRxiv2018

Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

BackgroundThe life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.\n\nResultIn the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.\n\nConclusionOur study will provide a foundation for future studies to explore this key epigenetic modification in development of Cysticercus cellulosae and in human cysticercus disease.

genetics↗