High-resolution transcriptome datasets during embryogenesis of plant-parasitic nematodes.

Understanding the transcriptional regulatory characteristics throughout the embryogenesis of plant-parasitic nematodes is crucial for elucidating their developmental processes' uniqueness. However, a challenge arises due to the lack of suitable technical methods for synchronizing the age of plant-parasitic nematodes embryo, it is difficult to collect detailed transcriptome data at each stage of embryonic development. Here, we recorded the 11 embryonic developmental time-points of endophytic nematode Meloidogyne incognita (isolated from Wuhan, China), Heterodera glycines (isolated from Wuhan, China), and Ditylenchus destructor (isolated from Jinan, China) species, and constructed transcriptome datasets of single embryos of these three species utilizing low-input smart-seq2 technology. The datasets encompassed 11 complete embryonic development stages, including Zygote, 2-cell, 4-cell, 8-cell, 24-44 cell, 64-78 cell, Comma, 1.5-fold, 2-fold, Moving, and L1, each stage generated four to five replicates, resulting in a total of 162 high-resolution transcriptome libraries. This high-resolution cross-species dataset serves as a crucial resource for comprehending the embryonic developmental properties of plant-parasitic nematodes and for identifying functional regulatory genes during embryogenesis.

KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity.

The BET family member BRD4 is a bromodomain-containing protein that plays a vital role in driving oncogene expression. Given their pivotal role in regulating oncogenic networks in various cancer types, BET inhibitors (BETi) have been developed, but the clinical application has been impeded by dose-limiting toxicity and resistance. Understanding the mechanisms of BRD4 activity and identifying predictive biomarkers could facilitate the successful clinical use of BETis. Herein, we show that KDM5C and BRD4 cooperate to sustain tumor cell growth. Mechanistically, KDM5C interacted with BRD4 and stimulated BRD4 enhancer recruitment. Moreover, binding of the BRD4 C-terminus to KDM5C stimulated the H3K4 demethylase activity of KDM5C. The abundance of both KDM5C-associated BRD4 and H3K4me1/3 determined the transcriptional activation of many oncogenes. Notably, depletion or pharmacologic degradation of KDM5C dramatically reduced BRD4 chromatin enrichment and significantly increased BETi efficacy across multiple cancer types in both tumor cell lines and patient-derived organoid models. Furthermore, targeting KDM5C in combination with BETi suppressed tumor growth in vivo in a xenograft mouse model. Collectively, this work reveals a KDM5C-mediated mechanism by which BRD4 regulates transcription, providing a rationale for incorporating BETi into combination therapies with KDM5C inhibitors to enhance treatment efficacy. SIGNIFICANCE: BRD4 is recruited to enhancers in a bromodomain-independent manner by binding KDM5C and stimulates KDM5C H3K4 demethylase activity, leading to synergistic effects of BET and KDM5C inhibitor combinations in cancer.

Unzipped chromosome-level genomes reveal allopolyploid nematode origin pattern as unreduced gamete hybridization.

The formation and consequences of polyploidization in animals with clonal reproduction remain largely unknown. Clade I root-knot nematodes (RKNs), characterized by parthenogenesis and allopolyploidy, show a widespread geographical distribution and extensive agricultural destruction. Here, we generated 4 unzipped polyploid RKN genomes and identified a putative novel alternative telomeric element. Then we reconstructed 4 chromosome-level assemblies and resolved their genome structures as AAB for triploid and AABB for tetraploid. The phylogeny of subgenomes revealed polyploid RKN origin patterns as hybridization between haploid and unreduced gametes. We also observed extensive chromosomal fusions and homologous gene expression decrease after polyploidization, which might offset the disadvantages of clonal reproduction and increase fitness in polyploid RKNs. Our results reveal a rare pathway of polyploidization in parthenogenic polyploid animals and provide a large number of high-precision genetic resources that could be used for RKN prevention and control.

In Silico Analysis Highlights the Diversity and Novelty of Circular Bacteriocins in Sequenced Microbial Genomes.

Consumer demand for "fresh food" with no chemical preservatives has prompted researchers to pay more attention to natural antimicrobial peptides such as bacteriocins. Nisin is currently the most widely used food biopreservative among the bacteriocins; however, its applications are restricted due to its low stability at neutral and alkaline pH values. Circular bacteriocins have potent antimicrobial activity against foodborne pathogens, show exceptional stability, and have great potential to be developed as biopreservatives. Here, we take advantage of the precursor peptides of 15 reported circular bacteriocins to devise an in silico approach to identify potential circular bacteriocins in sequenced microbial genomes. A total of nearly 7,000 putative precursor peptides were identified from 86 species of bacteria and further classified into 28 groups based on their amino acid similarity. Among the groups, 19 showed low similarity (less than 50%) to any known precursor peptide of circular bacteriocins. One novel circular bacteriocin in group 11, cerecyclin, showed the highest identity (34%) to the known circular bacteriocin enterocin NKR-5-3B and was selected for verification. Cerecyclin showed antimicrobial activity against several Gram-positive bacteria, inhibited the outgrowth of Bacillus cereus spores, and did not exhibit hemolysis activity. Moreover, it showed 4-fold- to 8-fold-higher antimicrobial activity against B. cereus and Listeria monocytogenes than nisin A. Cerecyclin also had increased stability compared to nisin A under neutral or alkaline conditions. This work not only identified a promising food biopreservative but also provided a rich source for novel circular bacteriocins.IMPORTANCE Circular bacteriocins are promising biopreservatives, and it is important to identify more novel circular bacteriocins to enhance the current arsenal of antimicrobials. In this study, we used an in silico approach to identify a large number of novel circular bacteriocins and classified these bacteriocins into 28 groups rather than the 2 groups that were described in previous studies. Nineteen groups were novel and had low similarity (less than 50%) to any known precursor peptides of circular bacteriocins; this finding greatly expands the awareness of the novelty and diversity of circular bacteriocins. A novel circular bacteriocin which we named cerecyclin was identified in the B. cereus group; this circular bacteriocin had great antimicrobial activity against some foodborne pathogens and showed extreme stability. This study not only identified a promising food biopreservative but also provided a rich source for the identification of novel circular bacteriocins and the development of new biopreservatives.

The CRISPR-Cas systems were selectively inactivated during evolution of Bacillus cereus group for adaptation to diverse environments.

CRISPR-Cas systems are considered as barriers to horizontal gene transfer (HGT). However, the influence of such systems on HGT within species is unclear. Also, little is known about the impact of CRISPR-Cas systems on bacterial evolution at the population level. Here, using Bacillus cereus sensu lato as model, we investigate the interplay between CRISPR-Cas systems and HGT at the population scale. We found that only a small fraction of the strains have CRISPR-Cas systems (13.9% of 1871), and most of such systems are defective based on their gene content analysis. Comparative genomic analysis revealed that the CRISPR-Cas systems are barriers to HGT within this group, since strains harboring active systems contain less mobile genetic elements (MGEs), have lower fraction of unique genes and also display limited environmental distributions than strains without active CRISPR-Cas systems. The introduction of a functional CRISPR-Cas system into a strain lacking the system resulted in reduced adaptability to various stresses and decreased pathogenicity of the transformant strain, indicating that B. cereus group strains could benefit from inactivating such systems. Our work provides a large-scale case to support that the CRISPR-Cas systems are barriers to HGT within species, and that in the B. cereus group the inactivation of CRISPR-Cas systems correlated with acquisition of MGEs that could result in better adaptation to diverse environments.