Construction of Coarse-Grained Molecular Dynamics Model of Nuclear Global Chromosomes Dynamics in Mammalian Cells.

Biomolecules contain various heterogeneities in their structures and local chemical properties, and their functions emerge through the dynamics encoded by these heterogeneities. Molecular dynamics model-based studies will greatly contribute to the elucidation of such chemical/mechanical structure-dynamics-function relationships and the mechanisms that generate them. Coarse-grained molecular dynamics models with appropriately designed nonuniform local interactions play an important role in considering the various phenomena caused by large molecular complexes consisting of various proteins and DNA such as nuclear chromosomes. Therefore, in this chapter, we will introduce a method for constructing a coarse-grained molecular dynamics model that simulates the global behavior of each chromosome in the nucleus of a mammalian cell containing many giant chromosomes.

Congenital hereditary endothelial dystrophy with progressive sensorineural deafness: a case report of Harboyan syndrome

ABSTRACT We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.

Integrative morphological, cytogenetic and molecular characterization of the Andean climbing catfish Astroblepus mindoensis (Regan, 1916) (Siluriformes:Astroblepidae).

Astroblepus species, commonly known as Andean climbing catfish, exhibit a unique challenge in species delimitation, leading to ongoing taxonomic debates. Here we report data on Astroblepus mindoensis, a vulnerable species endemic to Ecuador, obtained by an integrative approach that includes cytogenetic analysis, molecular identification of the specimens, and recording of morphological and morphometric characters useful for species diagnosis. Thus, this study aimed to associate the karyotype data of the specimens analyzed with morphological and molecular characters, improving and expanding the existing taxonomic information, thus contributing to the systematics of the species. Our morphology results, unlike Regan's original description, which is brief and ambiguous, provide a more detailed morphometric and meristic description. Molecular phylogenetic reconstruction and genetic distance based on a fragment of the cytochrome c oxidase subunit I (COI) showed that our samples constitute a well-supported and monophyletic clade within the A. grixalvii species complex. The cytogenetic analysis identified distinct chromosomal markers, including a single cluster of major ribosomal genes (on chromosome pair 3) and of minor ribosomal genes (on chromosome pair 12) with their localization differing from those reported in other Astroblepus species analyzed. Additionally, the presence of a heteromorphic chromosome pair in males suggests the presence of an XX/XY sex-determination system that has not been identified in other congeneric species. Further investigation is necessary to determine if these chromosomes are associated with the accumulation of repeated sequences, as typically occurs with sex chromosomes, and to assess their presence in other species of the genus.

Dinochromosome Heterotermini with Telosomal Anchorages.

Dinoflagellate birefringent chromosomes (BfCs) contain some of the largest known genomes, yet they lack typical nucleosomal micrococcal-nuclease protection patterns despite containing variant core histones. One BfC end interacts with extranuclear mitotic microtubules at the nuclear envelope (NE), which remains intact throughout the cell cycle. Ultrastructural studies, polarized light and fluorescence microscopy, and micrococcal nuclease-resistant profiles (MNRPs) revealed that NE-associated chromosome ends persisted post-mitosis. Histone H3K9me3 inhibition caused S-G2 delay in synchronous cells, without any effects at G1. Differential labeling and nuclear envelope swelling upon decompaction indicate an extension of the inner compartment into telosomal anchorages (TAs). Additionally, limited effects of low-concentration sirtinol on bulk BfCs, coupled with distinct mobility patterns in MNase-digested and psoralen-crosslinked nuclei observed on 2D gels, suggest that telomeric nucleosomes (TNs) are the primary histone structures. The absence of a nucleosomal ladder with cDNA probes, the presence of histone H2A and telomere-enriched H3.3 variants, along with the immuno-localization of H3 variants mainly at the NE further reinforce telomeric regions as the main nucleosomal domains. Cumulative biochemical and molecular analyses suggest that telomeric repeats constitute the major octameric MNRPs that provision chromosomal anchorage at the NE.

LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling.

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.

Distribution Of Microrna Counts Across Human Chromosomes.

INTRODUCTION: microRNAs (miRNAs) are a class of non-coding RNAs that play important roles in gene regulation. miRNAs are transcribed from DNA sequences into primary miRNAs and then processed into precursor miRNAs and mature miRNAs. miRNA gene counts in chromosomes for different species have been studied. METHOD: Certain chromosomes have higher numbers of miRNA genes in all species, such as the X chromosome, while the Y chromosome has the fewest or no miRNA genes. miRNA counts in different chromosomes might have a positive correlation with coding gene counts in many species. In this study, a regression model was used to find the relationship between the miRNA count and the coding gene count across human chromosomes, and miRNA counts for 23 human chromosomes were predicted based on this regression model. In addition, the chromosome locations for the miRNA biomarkers of major depression, diabetes, Parkinson's disease, and COVID-19 are discussed. RESULTS: The results reveal that miRNA biomarkers of these diseases are located in various chromosomes. The dispersion of miRNA locations across different chromosomes might explain the complication of the pathology of these diseases. Moreover, diabetes and COVID-19 have the largest number of miRNA biomarkers from Chromosome X. CONCLUSION: As Chromosome X is a sex chromosome, this phenomenon may explain the gender difference in the prevalence or severity of diabetes and COVID-19. The significant gender difference in the prevalence or severity of diabetes and COVID-19 might be due to the regulation function of their miRNA biomarkers from Chromosome X.

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.

Heat Shock Factor 1 forms nuclear condensates and restructures the yeast genome before activating target genes.

In insects and mammals, 3D genome topology has been linked to transcriptional states yet whether this link holds for other eukaryotes is unclear. Using both ligation proximity and fluorescence microscopy assays, we show that in Saccharomyces cerevisiae, Heat Shock Response (HSR) genes dispersed across multiple chromosomes and under the control of Heat Shock Factor (Hsf1) rapidly reposition in cells exposed to acute ethanol stress and engage in concerted, Hsf1-dependent intergenic interactions. Accompanying 3D genome reconfiguration is equally rapid formation of Hsf1-containing condensates. However, in contrast to the transience of Hsf1-driven intergenic interactions that peak within 10-20 min and dissipate within 1 hr in the presence of 8.5% (v/v) ethanol, transcriptional condensates are stably maintained for hours. Moreover, under the same conditions, Pol II occupancy of HSR genes, chromatin remodeling, and RNA expression are detectable only later in the response and peak much later (>1 hr). This contrasts with the coordinate response of HSR genes to thermal stress (39°C) where Pol II occupancy, transcription, histone eviction, intergenic interactions, and formation of Hsf1 condensates are all rapid yet transient (peak within 2.5-10 min and dissipate within 1 hr). Therefore, Hsf1 forms condensates, restructures the genome and transcriptionally activates HSR genes in response to both forms of proteotoxic stress but does so with strikingly different kinetics. In cells subjected to ethanol stress, Hsf1 forms condensates and repositions target genes before transcriptionally activating them.

Trans regulation of an odorant binding protein by a proto-Y chromosome affects male courtship in house fly.

The male-limited inheritance of Y chromosomes favors alleles that increase male fitness, often at the expense of female fitness. Determining the mechanisms underlying these sexually antagonistic effects is challenging because it can require studying Y-linked alleles while they still segregate as polymorphisms. We used a Y chromosome polymorphism in the house fly, Musca domestica, to address this challenge. Two male determining Y chromosomes (YM and IIIM) segregate as stable polymorphisms in natural populations, and they differentially affect multiple traits, including male courtship performance. We identified differentially expressed genes encoding odorant binding proteins (in the Obp56h family) as candidate agents for the courtship differences. Through network analysis and allele-specific expression measurements, we identified multiple genes on the house fly IIIM chromosome that could serve as trans regulators of Obp56h gene expression. One of those genes is homologous to Drosophila melanogaster CG2120, which encodes a transcription factor that binds near Obp56h. Upregulation of CG2120 in D. melanogaster nervous tissues reduces copulation latency, consistent with this transcription factor acting as a negative regulator of Obp56h expression. The transcription factor gene, which we name speed date, demonstrates a molecular mechanism by which a Y-linked gene can evolve male-beneficial effects.

SMC4 serves as a potential marker for the diagnosis and prognosis of colon adenocarcinoma.

OBJECTIVE: We aimed to explore the role of structural maintenance of chromosomes 4 (SMC4) in malignant progression and immunology of colon adenocarcinoma (COAD). METHODS: The expression, genetic and protein features, and immune cell infiltration of SMC4 in pan-cancer were provided by public databases and websites. The protein expression of SMC4 in COAD tissues was screened by immunohistochemical assay. Si-RNA-mediated transfection was performed in COAD cells and the proliferation viability was measured using MTT, colony formation and EdU assays. Cell autophagy was detected by AO staining, western blots, and immunofluorescence staining. The migratory ability was determined using scratch and transwell assays. The expression of epithelial-to-mesenchymal transition (EMT) markers and transcriptional factors were detected using western blots. RESULTS: The expression of SMC4 was upregulated in pan-cancer and had relationships with prognosis, TMB, and MSI of cancer patients. Particularly, SMC4 protein was highly expressed in COAD tissues and correlated with poor prognosis of patients. Depletion of SMC4 inhibited cell proliferation, induced autophagy, and decreased migration through EMT progression in COAD cells. In addition, SMC4 was associated with infiltration of neutrophils, M2 macrophages, and CD4 + T cells in COAD, and had positive association with M2 macrophage markers and immune checkpoints. CONCLUSION: SMC4 was correlated with patients' poor prognosis, proliferation, metastasis, and immune cell infiltrates, and might function as a potential diagnosis and prognostic biomarker in COAD.

The effect of T. aestivum chromosomes 1A and 1D on fertility of alloplasmic recombinant (H. vulgare)-T. aestivum lines depending on cytonuclear compatibility.

The effect of T. aestivum L. chromosomes 1A and 1D on fertility of recombinant bread wheat allolines of the same origin carrying the cytoplasm of barley H. vulgare L. and different levels of cytonuclear compatibility was studied. Alloline L-56 included mainly fully sterile (FS) and partially sterile (PS) plants, alloline L-57 included partially fertile (PF) plants and line L-58 included fertile (F) ones. Analysis of morphobiological traits and pollen painting indicated complete or partial male sterility in plants of allolines L-56 and L-57. To differentiate genotypes with cytonuclear coadaptation and genotypes with cytonuclear incompatibility, PCR analysis of the 18S/5S mitochondrial (mt) repeat was performed. Heteroplasmy (simultaneous presence of barley and wheat mtDNA copies) was found in FS, PS, PF and some F plants, which was associated with a violation of cytonuclear compatibility. Wheat-type homoplasmy (hm) was detected in the majority of the fertile plants, which was associated with cytonuclear coadaptation. The allolines used as maternal genotypes were crossed with wheat-rye substitution lines 1R(1A) and 1R(1D). In F1, all plants of PF×1R(1A) and PF×1R(1D) combinations were fertile, and in F2, a segregation close to 3 (fertile) : 1 (sterile) was observed. These results showed for the first time that chromosomes 1A and 1D carry one dominant Rf gene, which controls the restoration of male fertility of bread wheat carrying the cytoplasm of H. vulgare. All plants of F1 combinations FS×1R(1A), FS×1R(1D), PS×1R(1A), PS×1R(1D) were sterile, which indicates that a single dose of genes localized on wheat chromosomes 1A or 1D is not enough to restore male fertility in FS and PS plants. All plants of hybrid combinations F(hm)×1R(1A) and F(hm)×1R(1D) in both F1 and F2 were fertile, that is, fertility of allolines with cytonuclear coadaptation does not depend on wheat chromosomes 1A and 1D.

Karyotype's Rearrangement in Some Hybrids of the Orchidinae Subtribe.

Based on our karyological findings in the Anacamptis Rich., Ophrys L., and Serapias L. genera, we have identified chromosomal markers within some hybrids and elucidated their interrelationships. Mitotic chromosomes of fifteen taxa were analyzed using the conventional Feulgen staining method. Only for Anacamptis ×gennarii (Rchb. f.) H.Kretzschmar, Eccarius & Dietr. [A. morio (L.) R.M.Bateman, Pridgeon & M.W.Chase × A. papilionacea (L.) R.M.Bateman, Pridgeon & M.W.Chase] and its parental species were some data obtained and reported with the banding method with Giemsa, Hoechst 33258 fluorochrome, and the FISH techniques. Our research involved new chromosomal measurements of fifteen taxa, including six hybrids, along with schematic representations. Morphometric parameters, i.e., MCA and CVCL, were used to evaluate karyotype asymmetry. Of meaning were the analyses performed on chromosomal complements of selected hybrids, which distinctly revealed marker chromosomes present in one or both putative parental species. Among the parents identified in some hybrids, Ophrys tenthredinifera Willd. has shown some interest due to the presence in its karyotype of a pair of chromosomes (n.1) showing a notable secondary constriction on the long arm. Indeed, one of the homologs is clearly distinguishable in the analyzed hybrids, where it clearly emerges as one of the putative parents. Given the challenges in detecting certain karyomorphological features within the Orchidinae subtribe using alternative methods, such as Giemsa C-banding or fluorescence banding, the Feulgen method remains valuable for cytogenetic characterization. It helps us to understand the genomes of hybrids and parental species, thus contributing to a deeper understanding of their genetic composition.

Plant kinetochore complex: composition, function, and regulation.

The kinetochore complex, an important protein assembly situated on the centromere, plays a pivotal role in chromosome segregation during cell division. Like in animals and fungi, the plant kinetochore complex is important for maintaining chromosome stability, regulating microtubule attachment, executing error correction mechanisms, and participating in signaling pathways to ensure accurate chromosome segregation. This review summarizes the composition, function, and regulation of the plant kinetochore complex, emphasizing the interactions of kinetochore proteins with centromeric DNAs (cenDNAs) and RNAs (cenRNAs). Additionally, the applications of the centromeric histone H3 variant (the core kinetochore protein CENH3, first identified as CENP-A in mammals) in the generation of ploidy-variable plants and synthesis of plant artificial chromosomes (PACs) are discussed. The review serves as a comprehensive roadmap for researchers delving into plant kinetochore exploration, highlighting the potential of kinetochore proteins in driving technological innovations in synthetic genomics and plant biotechnology.

Comparative cytogenetics of three Zoraptera species as a basis for understanding chromosomal evolution in Polyneoptera insects.

Zoraptera (also called "angel insects") is one of the most unexplored insect orders. However, it holds promise for understanding the evolution of insect karyotypes and genome organization given its status as an early branching group of Polyneoptera and Pterygota (winged insects) during the Paleozoic. Here, we provide karyotype descriptions of three Zorapteran species: Brazilozoros huxleyi (2n♂; ♀ = 42; 42), B. kukalovae (2n♂; ♀ = 43; 44) and Latinozoros cacaoensis (2n♂; ♀ = 36; 36). These species represent two of the four recently recognized Zorapteran subfamilies. Contrary to an earlier suggestion that Zoraptera has holocentric chromosomes, we found karyotypes that were always monocentric. Interestingly, we detected both X0 (B. kukalovae) and XY (B. huxleyi, L. cacaoensis) sex chromosome systems. In addition to conventional karyotype descriptions, we applied fluorescent in situ hybridization for the first time in Zoraptera to map karyotype distributions of 18S rDNA, histone H3 genes, telomeres and (CAG)n and (GATA)n microsatellites. This study provides a foundation for cytogenetic research in Zoraptera.

The Smc5/6 complex counteracts R-loop formation at highly transcribed genes in cooperation with RNase H2.

The R-loop is a common transcriptional by-product that consists of an RNA-DNA duplex joined to a displaced strand of genomic DNA. While the effects of R-loops on health and disease are well established, there is still an incomplete understanding of the cellular processes responsible for their removal from eukaryotic genomes. Here, we show that a core regulator of chromosome architecture -the Smc5/6 complex- plays a crucial role in the removal of R-loop structures formed during gene transcription. Consistent with this, budding yeast mutants defective in the Smc5/6 complex and enzymes involved in R-loop resolution show strong synthetic interactions and accumulate high levels of RNA-DNA hybrid structures in their chromosomes. Importantly, we demonstrate that the Smc5/6 complex acts on specific types of RNA-DNA hybrid structures in vivo and promotes R-loop degradation by the RNase H2 enzyme in vitro. Collectively, our results reveal a crucial role for the Smc5/6 complex in the removal of toxic R-loops formed at highly transcribed genes and telomeres.

Alignment of a Trivalent Chromosome on the Metaphase Plate Is Associated with Differences in Microtubule Density at Each Kinetochore.

Chromosome alignment on the metaphase plate is a conserved phenomenon and is an essential function for correct chromosome segregation for many organisms. Organisms with naturally-occurring trivalent chromosomes provide a useful system for understanding how chromosome alignment is evolutionarily regulated, as they align on the spindle with one kinetochore facing one pole and two facing the opposite pole. We studied chromosome alignment in a praying mantid that has not been previously studied chromosomally, the giant shield mantis Rhombodera megaera. R. megaera has a chromosome number of 2n = 27 in males. Males have X1, X2, and Y chromosomes that combine to form a trivalent in meiosis I. Using live-cell imaging of spermatocytes in meiosis I, we document that sex trivalent Y chromosomes associate with one spindle pole and the two X chromosomes associate with the opposing spindle pole. Sex trivalents congress alongside autosomes, align with them on the metaphase I plate, and then the component chromosomes segregate alongside autosomes in anaphase I. Immunofluorescence imaging and quantification of brightness of kinetochore-microtubule bundles suggest that the X1 and X2 kinetochores are associated with fewer microtubules than the Y kinetochore, likely explaining the alignment of the sex trivalent at the spindle equator with autosomes. These observations in R. megaera support the evolutionary significance of the metaphase alignment of chromosomes and provide part of the explanation for how this alignment is achieved.

Length-sensitive partitioning of Caenorhabditiselegans meiotic chromosomes responds to proximity and number of crossover sites.

Sensing and control of size are critical for cellular function and survival. A striking example of size sensing occurs during meiosis in the nematode Caenorhabditis elegans. C. elegans chromosomes compare the lengths of the two chromosome "arms" demarcated by the position of their single off-center crossover, and they differentially modify these arms to ensure that sister chromatid cohesion is lost specifically on the shorter arm in the first meiotic division, while the longer arm maintains cohesion until the second division. While many of the downstream steps leading to cohesion loss have been characterized, the length-sensing process itself remains poorly understood. Here, we have used cytological visualization of short and long chromosome arms, combined with quantitative microscopy, live imaging, and simulations, to investigate the principles underlying length-sensitive chromosome partitioning. By quantitatively analyzing short-arm designation patterns on fusion chromosomes carrying multiple crossovers, we develop a model in which a short-arm-determining factor originates at crossover designation sites, diffuses within the synaptonemal complex, and accumulates within crossover-bounded chromosome segments. We demonstrate experimental support for a critical assumption of this model: that crossovers act as boundaries to diffusion within the synaptonemal complex. Further, we develop a discrete simulation based on our results that recapitulates a wide variety of observed partitioning outcomes in both wild-type and previously reported mutants. Our results suggest that the concentration of a diffusible factor is used as a proxy for chromosome length, enabling the correct designation of short and long arms and proper segregation of chromosomes.

Regulatory genome annotation of 33 insect species.

Annotation of newly sequenced genomes frequently includes genes, but rarely covers important non-coding genomic features such as the cis-regulatory modules-e.g., enhancers and silencers-that regulate gene expression. Here, we begin to remedy this situation by developing a workflow for rapid initial annotation of insect regulatory sequences, and provide a searchable database resource with enhancer predictions for 33 genomes. Using our previously developed SCRMshaw computational enhancer prediction method, we predict over 2.8 million regulatory sequences along with the tissues where they are expected to be active, in a set of insect species ranging over 360 million years of evolution. Extensive analysis and validation of the data provides several lines of evidence suggesting that we achieve a high true-positive rate for enhancer prediction. One, we show that our predictions target specific loci, rather than random genomic locations. Two, we predict enhancers in orthologous loci across a diverged set of species to a significantly higher degree than random expectation would allow. Three, we demonstrate that our predictions are highly enriched for regions of accessible chromatin. Four, we achieve a validation rate in excess of 70% using in vivo reporter gene assays. As we continue to annotate both new tissues and new species, our regulatory annotation resource will provide a rich source of data for the research community and will have utility for both small-scale (single gene, single species) and large-scale (many genes, many species) studies of gene regulation. In particular, the ability to search for functionally related regulatory elements in orthologous loci should greatly facilitate studies of enhancer evolution even among distantly related species.

High prevalence of chromosome 17 in breast cancer micronuclei: a means to get rid of tumor suppressors?

Micronuclei (MN), defined as small extra-nuclear chromatin bodies enclosed by a nuclear envelope, serve as noticeable markers of chromosomal instability (CIN). The MN have been used for breast cancer (BC) screening, diagnosis, and prognosis. However, more recently they have gained attention as seats for active chromosomal rearrangements. BC subtypes exhibit differential CIN levels and aggressiveness. This study aimed to investigate MN chromosomal contents across BC subtypes, exploring its potential role in aggressiveness and pathogenesis. Immunostaining of BC cells was performed with anti-centromeric antibody followed by confocal microscopy. Further, fluorescence in situ hybridization (FISH) was done to check the presence of specific chromosomes in the MN. The real time PCR was also done from the RNA isolated from MN to check the expression of TP53 gene. BC cell lines (CLs) showed the presence of both centromere-positive ( +) and -negative ( -) MN, with significant variation in frequency among hormone and human epidermal growth factor receptor positive and triple-negative (TN) BC cells. FISH targeting chromosomes 1, 3, 8, 11, and 17 detected centromeric signals for all the above chromosomes in MN with a relatively higher prevalence of chromosome 17 in all the CLs. Out of all the CLs, TNBC cells demonstrated the highest frequency of centromere + and chromosome 17 + MN. TP53 expression could also be demonstrated inside the MN by FISH and real time PCR. Patient sample imprints also confirmed the presence of chromosome 17 in MN with polysomy of the same in corresponding nuclei. The high prevalence of chromosome 17 in BC MN may connote the importance of its rearrangements in the pathogenesis of BC. Further, the higher prevalence of chromosome 17 and 1 signals in TNBC MN point towards the significance of pathogenetic events involving the genes located in these chromosomes in evolution of this more aggressive phenotype.

G6PC3 is involved in spermatogenesis by maintaining meiotic sex chromosome inactivation.

Meiosis, a process unique to germ cells, involves formation and repair of double-stranded nicks in DNA, pairing and segregation of homologous chromosomes, which ultimately achieves recombination of homologous chromosomes. Genetic abnormalities resulted from defects in meiosis are leading causes of infertility in humans. Meiotic sex chromosome inactivation (MSCI) plays a crucial role in the development of male germ cells in mammals, yet its underlying mechanisms remain poorly understood. In this study, we illustrate the predominant presence of a protein known as glucose 6 phosphatase catalyzed 3 (G6PC3) in pachytene spermatocytes, with a high concentration in the sex body (XY body), suggesting its significant involvement in male germ cell development. By employing CRISPR-Cas9 technology, we generate mice deficient in the G6pc3 gene, resulting in complete meiotic arrest at the pachytene stage in spermatocytes and are completely sterile. Additionally, we observe abnormal XY body formation and impaired MSCI in G6pc3-knockout spermatocytes. These findings underscore G6pc3 as a new essential regulator that is essential for meiotic progression. G6PC3 is involved in spermatocyte during male spermatogenesis development by the maintenance of meiosis chromosome silencing.