Search Results (29)

Paclobutrazol (PBZ) is a triazole-type plant growth regulator that interferes with gibberellin (GAs) biosynthesis by blocking the oxidation step that converts ent-kaurene into ent-kaurenoic acid; however, the developmental mechanisms linking GAs restriction with storage organ enlargement remain poorly understood. In potato, PBZ induces compact growth while promoting microtubers (MTs) expansion, suggesting that GAs depletion triggers coordinated developmental reprogramming rather than simply suppressing elongation. Here, we evaluated the phenotypic, histological, and transcriptomic responses associated with PBZ-induced MTs development in Solanum tuberosum L. PBZ treatment, which increased MTs size, suppressed stolon growth, and enhanced starch accumulation, indicating a shift toward storage tissue development. Transcriptomic analysis identified broad PBZ-responsive changes, including enrichment of pathways related to metabolism, ribosome function, carbon metabolism, plant hormone signaling, and cell cycle regulation. Network analyses revealed ATH1-associated modules connected with receptor-like kinases, transcriptional regulators, mitotic regulators, replication-licensing factors and condensin components, supporting coordinated regulation among growth control, localized proliferation, asymmetric division, endoreduplication, and chromatin stability. These patterns were further supported by the absence of a detectable gibberellic acid (GA₃) peak in PBZ-treated samples. These findings support a model in which PBZ-responsive signaling is associated with developmental reprogramming toward radial expansion and reinforcement of storage tissue, providing a regulatory mechanism by which growth repression is coupled to microtube enlargement in potato. Full article

Sex chromosome imbalance is a genetic challenge in species with unequal X-chromosome numbers. Organisms have developed distinct strategies to control this imbalance through a process called dosage compensation. These strategies include X-chromosome inactivation in mammals mediated by the XIST long noncoding RNA and proteins recruited by XIST, and X-linked hypertranscription in male Drosophila driven by the Male-Specific Lethal (MSL) complex. In Caenorhabditis elegans, gene expression is downregulated from each of the two X chromosomes of hermaphrodites by half, thereby matching the levels in XO males. This is mediated by a specialized condensin-containing protein complex, the Dosage Compensation Complex (DCC). In all cases, the chromatin states on the sex chromosomes must be first established and then maintained for the entire lifetime of the organism. Although mammals and nematodes both use repression to achieve dosage compensation, the mechanisms are very different. Here, we summarize recent advances on how repressive chromatin states are established and maintained, with a focus on contrasting C. elegans dosage compensation to XIST-mediated X-chromosome inactivation. We review how specialized chromosome topology, repressive chromatin modifications, and higher-order nuclear architecture are established and maintained to achieve sex-specific regulation of the X chromosomes and highlight key outstanding questions and future research directions. Full article

Quiescence is a reversible, non-proliferative cellular state that enables survival under nutrient limitation while preserving the capacity to resume growth. Rather than representing a passive default, quiescence is an actively regulated program conserved from unicellular eukaryotes to metazoans. This review focuses on the nuclear mechanisms underlying quiescence entry, maintenance, and exit, with primary emphasis on mechanistic insights from yeast models while highlighting conserved principles in multicellular systems. Across species, quiescence is characterized by global transcriptional repression, chromatin compaction, and the extensive reorganization of nuclear architecture, coordinated by nutrient-sensing pathways centered on TOR/mTOR signaling. We discuss how transcriptional reprogramming is achieved through redistribution of RNA polymerases, dynamic transcription factor activities, and large-scale remodeling of histone modifications, alongside repressive chromatin formation. In parallel, post-transcriptional mechanisms—including intron retention, alternative polyadenylation, and accumulation of non-coding RNAs—fine-tune gene expression while limiting biosynthetic output. We further examine how changes in nuclear organization, such as nucleolar condensation, condensin-mediated chromosome rearrangements, and telomere hyperclusters, support long-term viability and genome stability. Collectively, this review highlights nuclear dynamics as an integrative regulatory layer that links metabolic state to cellular identity, adaptability, and long-term survival, with broad implications for development, stem cell function, and disease. Full article

Cattle breeds are optimized either for milk or meat production and secrete consumed nutrients in the form of milk or accrete nutrients as skeletal muscle tissue, respectively. Surplus energy is usually stored in the form of fat in adipose tissues. To gain more insight into the physiological and genetic background of nutrient accretion as either protein or fat, an experimental F₂ population was generated crossing Charolais (CH) bulls and German Holstein (GH) cows. Mutations in two genes with known, profound effects on growth were segregating in this population: the I442M mutation in the non-SMC condensin I complex, subunit G (NCAPG) gene, and the Q204X mutation in the myostatin (MSTN) gene. The major aim of this study was to close the gap between the described effects of the NCAPG/LCORL region and MSTN SNPs on carcass and meat quality traits, as well as on the structure and composition of the underlying tissues. Whole carcass data, meat quality traits, composition of major cuts and their dominating muscles, including muscle and fat cell structure, were analyzed as well as chemical and fatty acid composition. Mutant alleles of both loci were associated with higher weights, increased muscularity, and reduced fatness, e.g., each explaining about 15% of the observed variance. However, both loci apparently affect traits in a specific manner, influencing either dimensional traits or mass accretion. Full article

Many cellular processes, including gene expression regulation, DNA replication and repair, as well as proper condensation and segregation of chromosomes, require highly coordinated remodeling of chromatin. Cohesin and condensins, the structural maintenance of chromosomes (SMC) protein complexes that function as ATP-powered loop extrusion motors, are key determinants of chromatin structure. The genetic loss of their function is lethal, whereas inducible degradation approaches enable rapid, robust analysis of the depletion phenotype. In this review, we discuss new insights into chromatin folding through each cell cycle phase from the auxin-inducible degradation (AID) system. We review the mechanisms by which condensins and cohesins contribute to the helical organization of mitotic chromosomes and to the maintenance of chromosome territories in interphase. Additionally, we discuss studies examining the roles of TOP2A, KIF4A, and SRBD during mitosis using the AID system. We then outline emerging principles of the mitotic-to-interphase transition and how targeted degradation of chromatin proteins reshapes this process. Finally, we highlight and discuss new advances in understanding interphase chromatin organization revealed by AID-based studies. Full article

Structural maintenance of chromosomes (SMC) complexes play a crucial role in organizing the three-dimensional structure of chromatin, facilitating key processes such as gene regulation, DNA repair, and chromosome segregation. This review explores the molecular mechanisms and biological significance of SMC-mediated loop extrusion complexes, including cohesin, condensins, and SMC5/6, focusing on their structure, their dynamic function during the cell cycle, and their impact on chromatin architecture. We discuss the implications of impairments in loop extrusion machinery as observed in experimental models and human diseases. Mutations affecting these complexes are linked to various developmental disorders and cancer, highlighting their importance in genome stability and transcriptional regulation. Advances in model systems and genomic techniques have provided deeper insights into the pathological roles of SMC complex dysfunction, offering potential therapeutic avenues for associated diseases. Full article

Structural Maintenance of Chromosomes (SMC) complexes are an evolutionary conserved protein family. In most eukaryotes, three SMC complexes have been characterized, as follows: cohesin, condensin, and SMC5/6 complexes. These complexes are involved in a plethora of functions, and defects in SMC genes can lead to an increased risk of chromosomal abnormalities, infertility, and cancer. To investigate the evolution of SMC complex genes in mammals, we analyzed their selective patterns in an extended phylogeny. Signals of positive selection were identified for condensin NCAPG, for two SMC5/6 complex genes (SMC5 and NSMCE4A), and for all cohesin genes with almost exclusive meiotic expression (RAD21L1, REC8, SMC1B, and STAG3). For the latter, evolutionary rates correlate with expression during female meiosis, and most positively selected sites fall in intrinsically disordered regions (IDRs). Our results support growing evidence that IDRs are fast evolving, and that they most likely contribute to adaptation through modulation of phase separation. We suggest that the natural selection signals identified in SMC complexes may be the result of different selective pressures: a host-pathogen arms race in the condensin and SMC5/6 complexes, and an intragenomic conflict for meiotic cohesin genes that is similar to that described for centromeres and telomeres. Full article

Chromatin is the complex of DNA and associated proteins found in the nuclei of living organisms. How it is organized is a major research field as it has implications for replication, repair, and gene expression. This review summarizes the current state of the chromatin organization field, with a special focus on chromatin motor complexes cohesin and condensin. Containing the highly conserved SMC proteins, these complexes are responsible for organizing chromatin during cell division. Additionally, research has demonstrated that condensin and cohesin also have important functions during interphase to shape the organization of chromatin and regulate expression of genes. Using the model organism C. elegans, the authors review the current knowledge of how these complexes perform such diverse roles and what open questions still exist in the field. Full article

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (−598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle. Full article

Transient DNA loops occur throughout the genome due to thermal fluctuations of DNA and the function of SMC complex proteins such as condensin and cohesin. Transient crosslinking within and between chromosomes and loop extrusion by SMCs have profound effects on high-order chromatin organization and exhibit specificity in cell type, cell cycle stage, and cellular environment. SMC complexes anchor one end to DNA with the other extending some distance and retracting to form a loop. How cells regulate loop sizes and how loops distribute along chromatin are emerging questions. To understand loop size regulation, we employed bead–spring polymer chain models of chromatin and the activity of an SMC complex on chromatin. Our study shows that (1) the stiffness of the chromatin polymer chain, (2) the tensile stiffness of chromatin crosslinking complexes such as condensin, and (3) the strength of the internal or external tethering of chromatin chains cooperatively dictate the loop size distribution and compaction volume of induced chromatin domains. When strong DNA tethers are invoked, loop size distributions are tuned by condensin stiffness. When DNA tethers are released, loop size distributions are tuned by chromatin stiffness. In this three-way interaction, the presence and strength of tethering unexpectedly dictates chromatin conformation within a topological domain. Full article

Persistent organic pollutants (POPs) are posing major environmental and health threats due to their stability, ubiquity, and bioaccumulation. Most of the numerous studies of these compounds deal with single chemicals, although real exposures always consist of mixtures. Thus, using different tests, we screened the effects on zebrafish larvae caused by exposure to an environmentally relevant POP mixture. Our mixture consisted of 29 chemicals as found in the blood of a Scandinavian human population. Larvae exposed to this POP mix at realistic concentrations, or sub-mixtures thereof, presented growth retardation, edemas, retarded swim bladder inflation, hyperactive swimming behavior, and other striking malformations such as microphthalmia. The most deleterious compounds in the mixture belong to the per- and polyfluorinated acids class, although chlorinated and brominated compounds modulated the effects. Analyzing the changes in transcriptome caused by POP exposure, we observed an increase of insulin signaling and identified genes involved in brain and eye development, leading us to propose that the impaired function of the condensin I complex caused the observed eye defect. Our findings contribute to the understanding of POP mixtures, their consequences, and potential threats to human and animal populations, indicating that more mechanistic, monitoring, and long-term studies are imperative. Full article

Adult height is inversely related to metabolic syndrome (MetS) risk, but its genetic impacts have not been revealed. The present study aimed to examine the hypothesis that adult height-related genetic variants interact with lifestyle to influence adult height and are associated with MetS risk in adults aged >40 in Korea during 2010–2014. Participants were divided into short stature (SS; control) and tall stature (TS; case) by the 85th percentile of adult height. The genetic variants linked to adult height were screened from a genome-wide association study in a city hospital-based cohort (n = 58,701) and confirmed in Ansan/Ansung plus rural cohorts (n = 13,783) among the Korean Genome and Epidemiology Study. Genetic variants that interacted with each other were identified using the generalized multifactor dimensionality reduction (GMDR) analysis. The interaction between the polygenic risk score (PRS) of the selected genetic variants and lifestyles was examined. Adult height was inversely associated with MetS, cardiovascular diseases, and liver function. The PRS, including zinc finger and BTB domain containing 38 (ZBTB38)_rs6762722, polyadenylate-binding protein-interacting protein-2B (PAIP2B)_rs13034890, carboxypeptidase Z (CPZ)_rs3756173, and latent-transforming growth factor beta-binding protein-1 (LTBP1)_rs4630744, was positively associated with height by 1.29 times and inversely with MetS by 0.894 times after adjusting for covariates. In expression quantitative trait loci, the gene expression of growth/differentiation factor-5 (GDF5)_rs224331, non-SMC condensin I complex subunit G (NCAPG)_rs2074974, ligand-dependent nuclear receptor corepressor like (LCORL)_rs7700107, and insulin-like growth factor-1 receptor (IGF1R)_rs2871865 was inversely linked to their risk allele in the tibial nerve and brain. The gene expression of PAIP2B_rs13034890 and a disintegrin and metalloproteinase with thrombospondin motifs-like-3 (ADAMTSL3)_rs13034890 was positively related to it. The PRS was inversely associated with MetS, hyperglycemia, HbA1c, and white blood cell counts. The wild type of GDF5_rs224331 (Ala276) lowered binding energy with rugosin A, D, and E (one of the hydrolyzable tannins) but not the mutated one (276Ser) in the in-silico analysis. The PRS interacted with energy intake and rice-main diet; PRS impact was higher in the high energy intake and the low rice-main diet. In conclusion, the PRS for adult height interacted with energy intake and diet patterns to modulate height and was linked to height and MetS by modulating their expression in the tibial nerve and brain. Full article

Mitotic chromosome assembly is an essential preparatory step for accurate transmission of the genome during cell division. During the past decades, biochemical approaches have uncovered the molecular basis of mitotic chromosomes. For example, by using cell-free assays of frog egg extracts, the condensin I complex central for the chromosome assembly process was first identified, and its functions have been intensively studied. A list of chromosome-associated proteins has been almost completed, and it is now possible to reconstitute structures resembling mitotic chromosomes with a limited number of purified factors. In this review, I introduce how far we have come in understanding the mechanism of chromosome assembly using cell-free assays and reconstitution assays, and I discuss their potential applications to solve open questions. Full article

Silver/silver chloride nanoparticles (Ag/AgCl NPs) are an alternative approach to control the larvae of Aedes aegypti, a vector of mosquito-borne diseases. However, the molecular mechanisms of Ag/AgCl NPs to A. aegypti have not been reported. In this work, Ag/AgCl NPs were synthesized using supernatant, mixed toxins from Bacillus thuringiensis subsp. israelensis (Bti), and heterologously expressed Cry4Aa and Cry4Ba toxins. The images from scanning electron microscopy revealed that the Ag/AgCl NPs were spherical in shape with a size range of 25–100 nm. The larvicidal activity against A. aegypti larvae revealed that the Ag/AgCl NPs synthesized using the supernatant of Bti exhibited higher toxicity (LC₅₀ = 0.133 μg/mL) than the Ag/AgCl NPs synthesized using insecticidal proteins (LC₅₀ = 0.148–0.217 μg/mL). The proteomic response to Ag/AgCl NPs synthesized using the supernatant of Bti in A. aegypti larvae was compared to the ddH₂O-treated control. Two-dimensional gel electrophoresis analysis revealed 110 differentially expressed proteins, of which 15 were selected for identification using mass spectrometry. Six upregulated proteins (myosin I heavy chain, heat shock protein 70, the F₀F₁-type ATP synthase beta subunit, methyltransferase, protein kinase, and condensin complex subunit 3) that responded to Ag/AgCl NP treatment in A. aegypti were reported for NP treatments in different organisms. These results suggested that possible mechanisms of action of Ag/AgCl NPs on A. aegypti larvae are: mitochondrial dysfunction, DNA and protein damage, inhibition of cell proliferation, and cell apoptosis. The findings from this work provide greater insight into the action of green synthesized Ag/AgCl NPs on the control of A. aegypti larvae. Full article

The entire genome becomes mobilized following DNA damage. Understanding the mechanisms that act at the genome level requires that we embrace experimental and computational strategies to capture the behavior of the long-chain DNA polymer, which is the building block for the chromosome. Long-chain polymers exhibit constrained, sub-diffusive motion in the nucleus. Cross-linking proteins, including cohesin and condensin, have a disproportionate effect on genome organization in their ability to stabilize transient interactions. Cross-linking proteins can segregate the genome into sub-domains through polymer–polymer phase separation (PPPS) and can drive the formation of gene clusters through small changes in their binding kinetics. Principles from polymer physics provide a means to unravel the mysteries hidden in the chains of life. Full article