Uveal melanoma (UM) is a deadly cancer that leads to metastatic disease in more than 50 % of the patients. Despite the improvement in the treatment of primary disease, there is still no effective therapy to prevent the development of metastases. Therefore, the disease requires intensive research to identify new treatment strategies. In preclinical UM models, epigenetic drugs have been shown to increase the sensitivity of resistant tumour cells to treatment. The successful use of histone deacetylase inhibitors, which induced cell cycle arrest, reprogramming consistent with melanocyte differentiation and inhibition of tumour growth in preclinical models, demonstrates the role of epigenetic regulation in UM metastasis. Identification of epigenetic changes associated with UM development an progression could contribute to the discovery of more effective drugs that, in combination with traditional approaches, may yield better therapeutic results for high-risk patients.

• Klíčová slova
• DNA methylation, epigenetic changes, histone modifications, malignant uveal melanoma, non-coding RNAs,
• MeSH
• epigeneze genetická MeSH
• lidé MeSH
• melanom * farmakoterapie   genetika   MeSH
• nádory kůže * MeSH
• nádory uvey * farmakoterapie   genetika   MeSH
• uveální melanom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Recent decades have seen a notable increase in cesarean section rates. Although lifesaving, cesarean delivery is associated with an elevated risk of adverse health outcomes in newborns, including respiratory diseases, atopic disorders, obesity, diabetes, and severe autoimmune conditions. The exact mechanisms underlying these associations remain elusive; however, epigenetic modifications have emerged as a plausible molecular basis linking perinatal factors with future disease susceptibility. This review summarizes current literature, revealing that the delivery method may influence epigenetic markers in neonates, primarily through alterations in global DNA methylation and gene-specific methylation patterns.

• Klíčová slova
• DNA methylation, Epigenetics, cesarean section,
• MeSH
• císařský řez * statistika a číselné údaje   MeSH
• epigeneze genetická * MeSH
• lidé MeSH
• metylace DNA * MeSH
• novorozenec MeSH
• těhotenství MeSH
• vedení porodu metody   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation.

• Klíčová slova
• Clear cell carcinoma, Endometrioid carcinoma, HNF-1-beta, Immunohistochemistry, Methylation, Mutation analysis,
• MeSH
• adenokarcinom z jasných buněk genetika   patologie   MeSH
• endometroidní karcinom genetika   patologie   MeSH
• epigeneze genetická genetika   MeSH
• epigenomika metody   MeSH
• genetická variace genetika   MeSH
• hepatocytární jaderný faktor 1-beta genetika   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory endometria genetika   patologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• serózní cystadenokarcinom genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH

In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.

• Klíčová slova
• DNA methylation, HPA axis, RNA, stress, transgenerational epigenetic inheritance, trauma,
• MeSH
• databáze genetické MeSH
• dědičnost * MeSH
• epigeneze genetická * genetika   MeSH
• savci genetika   MeSH
• typy dědičnosti MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

At the molecular scale, adaptive advantages during plant growth and development rely on modulation of gene expression, primarily provided by epigenetic machinery. One crucial part of this machinery is histone posttranslational modifications, which form a flexible system, driving transient changes in chromatin, and defining particular epigenetic states. Posttranslational modifications work in concert with replication-independent histone variants further adapted for transcriptional regulation and chromatin repair. However, little is known about how such complex regulatory pathways are orchestrated and interconnected in cells. In this work, we demonstrate the utility of mass spectrometry-based approaches to explore how different epigenetic layers interact in Arabidopsis mutants lacking certain histone chaperones. We show that defects in histone chaperone function (e.g., chromatin assembly factor-1 or nucleosome assembly protein 1 mutations) translate into an altered epigenetic landscape, which aids the plant in mitigating internal instability. We observe changes in both the levels and distribution of H2A.W.7, altogether with partial repurposing of H3.3 and changes in the key repressive (H3K27me1/2) or euchromatic marks (H3K36me1/2). These shifts in the epigenetic profile serve as a compensatory mechanism in response to impaired integration of the H3.1 histone in the fas1 mutants. Altogether, our findings suggest that maintaining genome stability involves a two-tiered approach. The first relies on flexible adjustments in histone marks, while the second level requires the assistance of chaperones for histone variant replacement.

• Klíčová slova
• Arabidopsis, chromatin remodeling, histone chaperone complex, histone variants, immunochemistry, mass spectrometry, post-translational modifications,
• MeSH
• Arabidopsis * genetika   metabolismus   MeSH
• epigeneze genetická * MeSH
• faktor 1 pro uspořádání chromatinu metabolismus   genetika   MeSH
• histonové chaperony * metabolismus   genetika   MeSH
• histony * metabolismus   MeSH
• mutace MeSH
• posttranslační úpravy proteinů MeSH
• proteiny huseníčku * metabolismus   genetika   MeSH
• regulace genové exprese u rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 1 pro uspořádání chromatinu MeSH
• histonové chaperony * MeSH
• histony * MeSH
• proteiny huseníčku * MeSH

BACKGROUND: Radiation therapy plays a leading role in the treatment of prostate cancer, but the emergence of radioresistant forms of this disease dictates the need for a personalized ap-proach based on the data from genetic and epigenetic markers. Such markers include the copy number variation as well as gene and microRNA expression. PURPOSE: The aim of the study was to validate the list of potential predictors of radioresistance of prostate tumor cells in a model experiment based on the determination of gene copy number variation, gene transcriptional activity and microRNA expression. MATERIAL AND METHODS: The study used a PC-3 prostate cancer cell culture. The determination of the relative copy number variation and expression of 32 genes (BRCA1, BRCA2, PTEN, CASP3, CASP8, BAX, BCL2, CASP9, P53, MDM2, AKT1, ATM, BRIP1, CDK1, CDKN1B, CCND1, CCND3, FGFR2, KU70, RAD50, RAP80, Rif1, RNF168, TopBP1, HIST, H2AX, EXO1, XRCC4, RBBP8, EP300, LIG4, C-FLIP), as well as 15 microRNAs (let-7, miR15a/ 16, miR-17, miR-18a, miR-21, miR-24, miR-26b, miR-99a, miR-100, miR-101, miR-106a, miR-663a, miR-143, miR-145) was performed using the real-time quantitative polymerase chain reaction method. It was found that daily irradiation of PC-3 cells on a Novalis TX linear accelerator at doses of 6 and 7 Gy for 5 days leads to a significant decrease in the total number of cells and the number of viable cells. Nevertheless, after 5 days of irradiation, about 15% of the initial number of prostate tumor cells retained their viability, which is due to their special genetic and epigenetic characteristics: increased copy number and expression of genes BRCA2, CDK1, CDKN1B, H2AX, RAD50, XRCC4, RBBP8 and EP300 and reduced copy number and expression of CCND3, TP53, and BCL2 genes, as well as differential expression of six microRNAs (hsa-miR-18a-5p, hsa-miR-24-5p, hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-145-5p, hsa-let-7a-3p). CONCLUSION: This study enabled to identify genetic and epigenetic markers of prostate tumor cells resistance to radiation therapy.

• Klíčová slova
• DNA repair, Radiation therapy, apoptosis, cell culture, copy number variation of genes, micro-RNA, prostate cancer, radiotherapy, transcriptional activity of genes,
• MeSH
• epigeneze genetická MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádory prostaty * genetika   MeSH
• regulace genové exprese u nádorů MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• MIRN145 microRNA, human MeSH Prohlížeč

Hepatocyte nuclear factor 1 beta (HNF1B) is a transcription factor which plays a crucial role in nephronogenesis, and its germline mutations have been associated with kidney developmental disorders. However, the effects of HNF1B somatic exonic mutations and its role in the pathogenesis of kidney tumours has not yet been elucidated. Depending on the type of the tumour HNF1B may act as a tumour suppressor or oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using an immunohistochemical approach, and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B in 130 cases of renal tumours (121 renal cell carcinomas, 9 oncocytomas). In the subset of clear cell renal cell carcinoma (ccRCC), decreased HNF1B expression was associated with a higher tumour grade and higher T stage. The mutation analysis revealed no mutations in the analysed samples. Promoter methylation was detected in two ccRCCs and one oncocytoma. The results of our work on a limited sample set suggest that while in papillary renal cell carcinoma HNF1B functions as an oncogene, in ccRCC and chRCC it may act in a tumour suppressive fashion.

• MeSH
• epigeneze genetická genetika   MeSH
• epigenomika metody   MeSH
• hepatocytární jaderný faktor 1-beta genetika   MeSH
• karcinom z renálních buněk genetika   patologie   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• mutační analýza DNA metody   MeSH
• nádory ledvin genetika   patologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč

Irreversible genetic alterations underlying human diseases have been widely studied to date. However, it is evident that the potentially reversible epigenetic dysregulations may also have an important role in the disease origin. The studies of epigenetic mechanisms underlying disease onset, progression and pathogenesis have been performed in various human disorders. The epigenetic approaches may reveal useful markers for disease diagnostics, classification and prognostics as well as for progressive pharmacological treatment. This review summarizes the studies of epigenetic dysregulations including aberrant methylation, histone modifications and miRNA alterations in cancer as well as the studies of methylation changes and aberrant histone modifications in neurodegenerative, autoimmune, cardiovascular and other diseases. The imprinting disorders together with the emerging role of epigenetics in nutritional genomics, environment-organism interaction studies and in some other fields are also mentioned.

• MeSH
• epigeneze genetická genetika   fyziologie   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• metylace DNA genetika   fyziologie   MeSH
• mikro RNA genetika   MeSH
• nemoc genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• histony MeSH
• mikro RNA MeSH

Although epigenetic modifications have been intensely investigated over the last decade due to their role in crop adaptation to rapid climate change, it is unclear which epigenetic changes are heritable and therefore transmitted to their progeny. The identification of epigenetic marks that are transmitted to the next generations is of primary importance for their use in breeding and for the development of new cultivars with a broad-spectrum of tolerance/resistance to abiotic and biotic stresses. In this review, we discuss general aspects of plant responses to environmental stresses and provide an overview of recent findings on the role of transgenerational epigenetic modifications in crops. In addition, we take the opportunity to describe the aims of EPI-CATCH, an international COST action consortium composed by researchers from 28 countries. The aim of this COST action launched in 2020 is: (1) to define standardized pipelines and methods used in the study of epigenetic mechanisms in plants, (2) update, share, and exchange findings in epigenetic responses to environmental stresses in plants, (3) develop new concepts and frontiers in plant epigenetics and epigenomics, (4) enhance dissemination, communication, and transfer of knowledge in plant epigenetics and epigenomics.

• Klíčová slova
• abiotic stress, biotic stress, epigenetic, methodology, stress memory, transgenerational memory,
• MeSH
• aklimatizace genetika   MeSH
• epigeneze genetická MeSH
• epigenomika metody   MeSH
• fyziologická adaptace genetika   MeSH
• fyziologický stres genetika   MeSH
• metylace DNA MeSH
• regulace genové exprese u rostlin MeSH
• šlechtění rostlin metody   MeSH
• typy dědičnosti MeSH
• zemědělské plodiny genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Type 1 diabetes mellitus (T1DM) is caused by an autoimmune destruction of the pancreatic β-cells, a process in which autoreactive T cells play a pivotal role, and it is characterized by islet autoantibodies. Consequent hyperglycemia is requiring lifelong insulin replacement therapy. T1DM is caused by the interaction of multiple environmental and genetic factors. The integrations of environments and genes occur via epigenetic regulations of the genome, which allow adaptation of organism to changing life conditions by alternation of gene expression. T1DM has increased several-fold over the past half century. Such a short time indicates involvement of environment factors and excludes genetic changes. This review summarizes the most current knowledge of epigenetic changes in that process leading to autoimmune diabetes mellitus.

• Klíčová slova
• HLA class II, epigenetic modifications, insulin, type 1 diabetes,
• MeSH
• diabetes mellitus 1. typu genetika   MeSH
• epigeneze genetická * MeSH
• genetická predispozice k nemoci MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• regulace genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH