Histones are positively charged proteins found in the chromatin of eukaryotic cells. They regulate gene expression and are required for the organization and packaging of DNA within the nucleus. Histones are extremely conserved, allowing for transcription, replication, and repair. This review delves into their complex structure and function in DNA assembly, their role in nucleosome assembly, and the higher-order chromatin structures they generate. We look at the five different types of histone proteins: H1, H2A, H2B, H3, H4, and their variations. These histones bind with DNA to produce nucleosomes, the basic units of chromatin that are essential for compacting DNA and controlling its accessibility. Their dynamic control of chromatin accessibility has important implications for genomic stability and cellular activities. We elucidate regulatory mechanisms in both normal and pathological situations by investigating their structural features, diverse interaction mechanisms, and chromatin impact. In addition, we discuss the functions of histone post-translational modifications (PTMs) and their significance in various disorders. These alterations, which include methylation, acetylation, phosphorylation, and ubiquitination, are crucial in regulating histone function and chromatin dynamics. We specifically describe and explore the role of changed histones in the evolution of cancer, neurological disorders, sepsis, autoimmune illnesses, and inflammatory conditions. This comprehensive review emphasizes histone's critical role in genomic integrity and their potential as therapeutic targets in various diseases.

• Klíčová slova
• Chromatin, Disease, Gene expression, Genomic stability, Histones, Nucleosomes, Post-translational modifications (PTMs),
• MeSH
• chromatin metabolismus   genetika   chemie   MeSH
• DNA * metabolismus   chemie   MeSH
• genom MeSH
• histony * metabolismus   chemie   genetika   MeSH
• lidé MeSH
• nádory genetika   metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chromatin MeSH
• DNA * MeSH
• histony * MeSH

Interspecific hybridization leads to complex interactions between the parental genomes, often in the form of genome dominance, where one genome prevails over the other. This phenomenon has been attributed to differential chromosome behavior during meiotic division and may involve either female or male meiosis, or both. In hybrids of Allium cepa × A. roylei, only female meiosis is involved, favoring the transmission of A. roylei chromosomes; male meiosis leads to the development of gametes with equal proportion of parental genomes. Female meiotic drive shifts the genome composition from 8R (A. roylei) + 8C (A. cepa) chromosomes in F1 to 9.3R + 6.7C in F2. In this study of two successive backcross generations with A. cepa (BC1 [first backcross generation] and BC1F1 [progeny after intercross of the first backcross generation]), we observed a change in genome dominance: the A. roylei genome, initially dominant during the meiosis in the F1 hybrids, became submissive in BC1, resulting in a genome composition skewed toward A. cepa. Among 23 BC1 and 236 BC1F1 plants, we observed a significant deviating trend of gradual reduction in A. roylei chromosome representation. The reduction was higher in the lineages with more unequal starting proportion of the parental genomes. This study highlights the dynamic nature of genomic interactions in hybrids and raises questions about the underlying molecular mechanisms driving these changes in dominance, as well as the potential for manipulating these interactions for agricultural benefit. Further exploration of the chromosomal behavior during meiosis across various hybrids will deepen our understanding of non-Mendelian inheritance patterns and their implications in plant breeding.

• MeSH
• Allium genetika   MeSH
• česneky * genetika   MeSH
• chromozomy rostlin MeSH
• genom rostlinný * MeSH
• hybridizace genetická * MeSH
• meióza * MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The role of autologous hematopoietic stem cell transplantation (AHSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL) remains controversial. The aim of this retrospective study was to analyze results of AHSCT and to identify prognostic factors. METHODS: Overall, 700 patients transplanted in first complete remission between the years 1999-2020 were included. Median patient age was 31.9 years (68% male). B-cell precursor ALL (BCP-ALL) and T-cell precursor ALL (TCP-ALL) was diagnosed in 35% and 65%, respectively. Among 190 patients with available data, negative minimal residual disease (MRD) status was reported in 167 (88%) cases. RESULTS: The probabilities of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 67% and 56%; relapse incidence (RI) and non-relapse mortality (NRM) were 39% and 5%, respectively. TCP-ALL was associated with lower RI (41% vs. 56%, p=0.001), higher LFS (52% vs. 38%, p=0.002) and OS (58% vs 45%, p=0.001) at 5 years when compared to BCP-ALL. In the multivariate analysis, TCP-ALL and longer interval from diagnosis do AHSCT were associated with reduced risk of relapse (HR 0.7, p=0.006 and HR=0.95, p=0.018), better LFS (HR=0.76, p=0.02 and HR=0.95, p=0.01) and OS (HR=0.75, p=0.024 and HR=0.94, p=0.013, respectively). Increasing patient age was associated with higher NRM (HR=1.49, p<0.0001), worse LFS (HR=1.1, p=0.01) and OS (HR=1.17, p=0.0001). CONCLUSIONS: Autologous hematopoietic stem cell transplantation is relatively safe option of late treatment intensification in adults with Ph- ALL. It may be a valuable option especially in patients with TCP-ALL, however it should be proved in prospective clinical trials.

• Klíčová slova
• Autologous stem cell transplantation, Complete remission, Philadelphia negative acute lymphoblastic leukemia,
• MeSH
• akutní lymfatická leukemie * terapie   mortalita   MeSH
• autologní transplantace MeSH
• dospělí MeSH
• filadelfský chromozom MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• reziduální nádor MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Non-canonical (non-B) DNA structures-e.g. bent DNA, hairpins, G-quadruplexes (G4s), Z-DNA, etc.-which form at certain sequence motifs (e.g. A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies and occupy 9%-15%, 9%-11%, and 12%-38% of autosomes and chromosomes X and Y, respectively. G4s and Z-DNA are enriched at promoters and enhancers, as well as at origins of replication. Repetitive sequences harbor more non-B DNA motifs than non-repetitive sequences, especially in the short arms of acrocentric chromosomes. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.

• MeSH
• DNA * chemie   genetika   MeSH
• G-kvadruplexy MeSH
• genom lidský MeSH
• genom * MeSH
• Hominidae * genetika   MeSH
• lidé MeSH
• nukleotidové motivy MeSH
• Pan troglodytes genetika   MeSH
• repetitivní sekvence nukleových kyselin MeSH
• telomery * genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA * MeSH

Chromosomal rearrangements are fundamental evolutionary drivers leading to genomic diversification. African clawed frogs (genus Xenopus, subgenera Silurana and Xenopus) represent an allopolyploid model system with conserved chromosome numbers in species with the same ploidy within each subgenus. Two significant interchromosomal rearrangements have been identified: a translocation between chromosomes 9 and 2, found in subgenus Silurana, and a fusion between chromosomes 9 and 10, probably widespread in subgenus Xenopus. Here, we study the allotetraploid Xenopus pygmaeus (subgenus Xenopus) based on in-depth karyotype analysis using chromosome measurements and fluorescent in situ hybridization (FISH). We designed FISH probes for genes associated with translocation and fusion to test for the presence of the two main types of rearrangements. We also examined the locations of 5S and 28S ribosomal tandem repeats, with the former often associated with telomeric regions and the latter with nucleolus organizer regions (NORs). The translocation-associated gene mapping did not detect the translocation in X. pygmaeus, supporting the hypothesis that the translocation is restricted to Silurana, but instead identified a pericentromeric inversion on chromosome 2S. The fusion-associated gene mapping confirmed the fusion of chromosomes 9 and 10, supporting this fusion as an ancestral state in subgenus Xenopus. As expected, the 5S repeats were found predominantly in telomere regions on almost all chromosomes. The nucleolar 28S repeats were localized on chromosome 6S, a position previously found only in the closely related species X. parafraseri, whereas other, phylogenetically more distant species have NORs located on different chromosomes. We therefore hypothesize that a jumping mechanism could explain the relatively frequent changes in the location of NORs during Xenopus evolution.

• MeSH
• genom MeSH
• genová přestavba * MeSH
• hybridizace in situ fluorescenční MeSH
• karyotyp MeSH
• karyotypizace MeSH
• mapování chromozomů MeSH
• molekulární evoluce MeSH
• organizátor jadérka * genetika   MeSH
• translokace genetická MeSH
• Xenopus * genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The influence of t(v;22) sole, major route ACAs all (+8, n = 14; +Ph, n = 10; +19, n = 1), and -Y sole on progression-free survival. Survival curves are compared with those of patients with the standard t(9;22) translocation. Other ACAs or complex karyotypes did not influence survival.

• Klíčová slova
• additional chromosomal abnormalities, chronic myeloid leukemia, cytogenetics, prognosis,
• MeSH
• chromozomální aberace * MeSH
• chronická myeloidní leukemie * genetika   diagnóza   mortalita   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 22 genetika   MeSH
• lidské chromozomy, pár 9 genetika   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• senioři MeSH
• translokace genetická * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• dopisy MeSH

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.

• Klíčová slova
• human papillomavirus, next-generation sequencing, penile, squamous cell carcinoma, tumor mutational burden,
• MeSH
• ATM protein genetika   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• infekce papilomavirem MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory penisu * genetika   mortalita   patologie   virologie   MeSH
• prognóza MeSH
• proteiny vázající telomery MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shelterinový komplex MeSH
• spinocelulární karcinom * genetika   mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ATM protein, human MeSH Prohlížeč
• ATM protein MeSH
• CDKN2A protein, human MeSH Prohlížeč
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• nádorové biomarkery * MeSH
• nádorový supresorový protein p53 MeSH
• POT1 protein, human MeSH Prohlížeč
• proteiny vázající telomery MeSH
• shelterinový komplex MeSH
• TP53 protein, human MeSH Prohlížeč

Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. The mark is interpreted by epigenetic readers that assist transcription and safeguard chromatin fiber integrity. In Drosophila, the chromodomain protein MSL3 binds H3K36me3 at X-chromosomal genes to implement dosage compensation. The PWWP-domain protein JASPer recruits the JIL1 kinase to active chromatin on all chromosomes. Because depletion of K36me3 had variable, locus-specific effects on the interactions of those readers, we systematically studied K36 methylation in a defined cellular model. Contrasting prevailing models, we found that K36me1, K36me2, and K36me3 each contribute to distinct chromatin states. Monitoring the changing K36 methylation landscape upon depletion of the three methyltransferases Set2, NSD, and Ash1 revealed local, context-specific methylation signatures. Each methyltransferase governs K36 methylation in dedicated genomic regions, with minor overlaps. Set2 catalyzes K36me3 predominantly at transcriptionally active euchromatin. NSD places K36me2/3 at defined loci within pericentric heterochromatin and on weakly transcribed euchromatic genes. Ash1 deposits K36me1 at putative enhancers. The mapping of MSL3 and JASPer suggested that they bind K36me2 in addition to K36me3, which was confirmed by direct affinity measurement. This dual specificity attracts the readers to a broader range of chromosomal locations and increases the robustness of their actions.

• MeSH
• chromatin * metabolismus   MeSH
• DNA vazebné proteiny metabolismus   genetika   MeSH
• Drosophila melanogaster genetika   metabolismus   MeSH
• euchromatin metabolismus   genetika   MeSH
• heterochromatin metabolismus   genetika   MeSH
• histonlysin-N-methyltransferasa * metabolismus   genetika   MeSH
• histony * metabolismus   MeSH
• lysin metabolismus   MeSH
• metylace MeSH
• protein-serin-threoninkinasy MeSH
• proteiny Drosophily * metabolismus   genetika   MeSH
• transkripční faktory metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ASH1 protein, Drosophila MeSH Prohlížeč
• chromatin * MeSH
• DNA vazebné proteiny MeSH
• euchromatin MeSH
• heterochromatin MeSH
• histonlysin-N-methyltransferasa * MeSH
• histony * MeSH
• JIL-1 protein, Drosophila MeSH Prohlížeč
• lysin MeSH
• protein-serin-threoninkinasy MeSH
• proteiny Drosophily * MeSH
• transkripční faktory MeSH

BACKGROUND: Java combtail fish Belontia hasselti (Cuvier, 1831), a member of the Osphronemidae family, inhabits lakes and rivers throughout Southeast Asia and Sri Lanka. Previous cytogenetic research revealed it possesses a diploid chromosome number of 48 chromosomes with a female-heterogametic ZZ/ZW sex chromosome system, where the W chromosome is distinguishable as the only metacentric element in the complement. Female-heterogametic sex chromosome systems seem to be otherwise surprisingly rare in the highly diverse order Perciformes and, therefore, B. hasselti provides an important comparative model to evolutionary studies in this teleost lineage. To examine the level of sex chromosome differentiation in B. hasselti and the contribution of repetitive DNAs to this process we combined bioinformatic analyses with chromosomal mapping of selected repetitive DNA classes, and comparative genomic hybridization. RESULTS: By providing the first satellitome study in Perciformes, we herein identified 13 satellite DNA monomers in B. hasselti, suggesting a very low diversity of satDNA in this fish species. Using fluorescence in situ hybridization, we revealed detectable clusters on chromosomes only for four satellite DNA monomers. Together with the two mapped microsatellite motifs, the repeats primarily accumulated on autosomes, with no distinct clusters located on the sex chromosomes. Comparative genomic hybridization showed no region with accumulated female-specific or enriched repeats on the W chromosome. Telomeric repeats terminated all chromosomes, and no additional interstitial sites were detected. CONCLUSION: These data collectively indicate a low degree of sex chromosome differentiation in B. hasselti despite their considerable heteromorphy. Possible mechanisms that may underlie this pattern are discussed.

• Klíčová slova
• Fishes, Isochromosome, Molecular cytogenetics, Satellitome, Sex chromosome evolution, Teleostei,
• MeSH
• hybridizace in situ fluorescenční MeSH
• mapování chromozomů MeSH
• Perciformes * genetika   MeSH
• pohlavní chromozomy * genetika   MeSH
• repetitivní sekvence nukleových kyselin * genetika   MeSH
• satelitní DNA genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• satelitní DNA MeSH

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and their synaptonemal complex (SC) mediated stabilization. Here, we investigate factors that promote and coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor of HIM-17, previously shown to promote double-strand break formation. We found that loss of bra-2 impairs synapsis elongation without affecting homolog recognition, chromosome movement or SC maintenance. Epistasis analyses reveal previously unrecognized activities for HIM-17 in regulating homolog pairing and SC assembly in a partially overlapping manner with BRA-2. We show that removing bra-2 or him-17 restores nuclear clustering, recruitment of PLK-2 at the nuclear periphery, and abrogation of ectopic synapsis in htp-1 mutants, suggesting intact CHK-2-mediated signaling and presence of a barrier that prevents SC polymerization in the absence of homology. Our findings shed light on the regulatory mechanisms ensuring faithful pairing and synapsis.

• MeSH
• Caenorhabditis elegans * genetika   metabolismus   MeSH
• checkpoint kinasa 2 MeSH
• dvouřetězcové zlomy DNA MeSH
• meióza * MeSH
• mutace MeSH
• párování chromozomů * MeSH
• polo-like kinasy MeSH
• protein-serin-threoninkinasy metabolismus   genetika   MeSH
• proteiny buněčného cyklu metabolismus   genetika   MeSH
• proteiny Caenorhabditis elegans * metabolismus   genetika   MeSH
• segregace chromozomů MeSH
• synaptonemální komplex * metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• checkpoint kinasa 2 MeSH
• CHK-2 protein, C elegans MeSH Prohlížeč
• Htp-1 protein, C elegans MeSH Prohlížeč
• polo-like kinase 2, C elegans MeSH Prohlížeč
• polo-like kinasy MeSH
• protein-serin-threoninkinasy MeSH
• proteiny buněčného cyklu MeSH
• proteiny Caenorhabditis elegans * MeSH