'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Tue, 18 Jun 2024 09:35:41 EDT Tue, 18 Jun 2024 09:35:41 EDT jirtle@radonc.duke.edu james001@jirtle.com Evolution and advancements in genomics and epigenomics in OA research: How far we have come. Ramos YFM, Rice SJ, Ali SA, Pastrello C, Jurisica I, Rai MF, Collins KH, Lang A, Maerz T, Geurts J, Ruiz-Romero C, June RK, Thomas Appleton C, Rockel JS, Kapoor M
Osteoarthritis Cartilage (Jul 2024)

Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput "omic" technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics - including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease.]]>
Wed, 31 Dec 1969 19:00:00 EST
Phytocannabinoids in neuromodulation: From omics to epigenetics. Banerjee S, Saha D, Sharma R, Jaidee W, Puttarak P, Chaiyakunapruk N, Chaoroensup R
J Ethnopharmacol (Aug 2024)

Recent developments in metabolomics, transcriptomic and epigenetics open up new horizons regarding the pharmacological understanding of phytocannabinoids as neuromodulators in treating anxiety, depression, epilepsy, Alzheimer's, Parkinson's disease and autism.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenome-wide association study of long-term psychosocial stress in older adults. Opsasnick LA, Zhao W, Schmitz LL, Ratliff SM, Faul JD, Zhou X, Needham BL, Smith JA
Epigenetics (Dec 2024)

Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress ( = 2,689) from the Health and Retirement Study (mean age = 70.4 years), assessing DNA methylation (Illumina Infinium HumanMethylationEPIC Beadchip) at 789,656 CpG sites. For identified CpG sites, we conducted a formal mediation analysis to examine whether smoking, alcohol use, physical activity, and body mass index (BMI) mediate the relationship between stress and DNA methylation. Nine CpG sites were associated with psychosocial stress (all  < 9E-07; FDR q < 0.10). Additionally, health behaviours and/or BMI mediated 9.4% to 21.8% of the relationship between stress and methylation at eight of the nine CpGs. Several of the identified CpGs were in or near genes associated with cardiometabolic traits, psychosocial disorders, inflammation, and smoking. These findings support our hypothesis that psychosocial stress is associated with DNA methylation across the epigenome. Furthermore, specific health behaviours mediate only a modest percentage of this relationship, providing evidence that other mechanisms may link stress and DNA methylation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Advances in post-translational modifications and recurrent spontaneous abortion. Lai H, Yang Y, Zhang J
Gene (Jun 2024)

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy loss, which affects approximately 1-2 % of women's fertility. The etiology of RSA has not yet been fully revealed, which poses a great problem for clinical treatment. Post- translational modifications(PTMs) are chemical modifications that play a crucial role in the functional proteome. A considerable number of published studies have shown the relationship between post-translational modifications of various proteins and RSA. The study of PTMs contributes to elucidating the role of modified proteins in the pathogenesis of RSA, as well as the design of more effective diagnostic/prognostic tools and more targeted treatments. Most reviews in the field of RSA have only focused on RNA epigenomics research. The present review reports the latest research developments of PTMs related to RSA, such as glycosylation, phosphorylation, Methylation, Acetylation, Ubiquitination, etc.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genetic confounds of transgenerational epigenetic inheritance in mice. Sapozhnikov DM, Szyf M
Epigenetics (Dec 2024)

Transgenerational epigenetic inheritance in mammals remains a controversial phenomenon. A recent study by Takahashi et al. provides evidence for this mode of inheritance in mice by using a CRISPR/Cas9-based epigenetic editing technique to modify DNA methylation levels at specific promoters and then demonstrating the inheritance of the gain in methylation in offspring. In this technical commentary, we argue that the method used in the original study inherently amplifies the likelihood of genetic changes that thereafter lead to the heritability of epigenetic changes. We provide evidence that genetic changes from multiple sources do indeed occur in these experiments and explore several avenues by which these changes could be causal to the apparent inheritance of epigenetic changes. We conclude a genetic basis of inheritance cannot be ruled out and thus transgenerational epigenetic inheritance has not been adequately established by the original study.]]>
Wed, 31 Dec 1969 19:00:00 EST
Dysregulated expression of cholesterol biosynthetic genes in Alzheimer's disease alters epigenomic signatures of hippocampal neurons. Paiva I, Seguin J, Grgurina I, Singh AK, Cosquer B, Plassard D, Tzeplaeff L, Le Gras S, Cotellessa L, Decraene C, Gambi J, Alcala-Vida R, Eswaramoorthy M, Buée L, Cassel JC, Giacobini P, Blum D, Merienne K, Kundu TK, Boutillier AL
Neurobiol Dis (Aug 2024)

Aging is the main risk factor of cognitive neurodegenerative diseases such as Alzheimer's disease, with epigenome alterations as a contributing factor. Here, we compared transcriptomic/epigenomic changes in the hippocampus, modified by aging and by tauopathy, an AD-related feature. We show that the cholesterol biosynthesis pathway is severely impaired in hippocampal neurons of tauopathic but not of aged mice pointing to vulnerability of these neurons in the disease. At the epigenomic level, histone hyperacetylation was observed at neuronal enhancers associated with glutamatergic regulations only in the tauopathy. Lastly, a treatment of tau mice with the CSP-TTK21 epi-drug that restored expression of key cholesterol biosynthesis genes counteracted hyperacetylation at neuronal enhancers and restored object memory. As acetyl-CoA is the primary substrate of both pathways, these data suggest that the rate of the cholesterol biosynthesis in hippocampal neurons may trigger epigenetic-driven changes, that may compromise the functions of hippocampal neurons in pathological conditions.]]>
Wed, 31 Dec 1969 19:00:00 EST
AIMER: A SNP-independent software for identifying imprinting-like allelic methylated regions from DNA methylome. Luo Y, Zhou T, Liu D, Wang F, Zhao Q
Comput Struct Biotechnol J (Dec 2024)

Genomic imprinting is essential for mammalian growth and embryogenesis. High-throughput bisulfite sequencing accompanied with parental haplotype-specific information allows analysis of imprinted genes and imprinting control regions (ICRs) on a large scale. Currently, although several allelic methylated regions (AMRs) detection software were developed, methods for detecting imprinted AMRs is still limited. Here, we developed a SNP-independent statistical approach, AIMER, to detect imprinting-like AMRs. By using the mouse frontal cortex methylome as input, we demonstrated that AIMER performs very well in detecting known germline ICRs compared with other methods. Furthermore, we found the putative parental AMRs AIMER detected could be distinguished from sequence-dependent AMRs. Finally, we found a novel germline imprinting-like AMR using WGBS data from 17 distinct mouse tissue samples. The results indicate that AIMER is a good choice for detecting imprinting-like (parent-of-origin-dependent) AMRs. We hope this method will be helpful for future genomic imprinting studies. The Python source code for our project is now publicly available on both GitHub (https://github.com/ZhaoLab-TMU/AIMER) and Gitee (https://gitee.com/zhaolab_tmu/AIMER).]]>
Wed, 31 Dec 1969 19:00:00 EST
Interaction between MED12 and ΔNp63 activates basal identity in pancreatic ductal adenocarcinoma. Maia-Silva D, Cunniff PJ, Schier AC, Skopelitis D, Trousdell MC, Moresco P, Gao Y, Kechejian V, He XY, Sahin Y, Wan L, Alpsoy A, Liverpool J, Krainer AR, Egeblad M, Spector DL, Fearon DT, Dos Santos CO, Taatjes DJ, Vakoc CR
Nat Genet (Jun 2024)

The presence of basal lineage characteristics signifies hyperaggressive human adenocarcinomas of the breast, bladder and pancreas. However, the biochemical mechanisms that maintain this aberrant cell state are poorly understood. Here we performed marker-based genetic screens in search of factors needed to maintain basal identity in pancreatic ductal adenocarcinoma (PDAC). This approach revealed MED12 as a powerful regulator of the basal cell state in this disease. Using biochemical reconstitution and epigenomics, we show that MED12 carries out this function by bridging the transcription factor ΔNp63, a known master regulator of the basal lineage, with the Mediator complex to activate lineage-specific enhancer elements. Consistent with this finding, the growth of basal-like PDAC is hypersensitive to MED12 loss when compared to PDAC cells lacking basal characteristics. Taken together, our genetic screens have revealed a biochemical interaction that sustains basal identity in human cancer, which could serve as a target for tumor lineage-directed therapeutics.]]>
Wed, 31 Dec 1969 19:00:00 EST
DNA methylation variation and growth in the clonal is regulated by both past and present lead environments. Quan J, Song S, Xing L, Liu X, Yue M
Epigenetics (Dec 2024)

Studies suggest that clonal plants' ability to select habitats and forage in a heterogeneous environment is influenced by their past environment, with stress legacy potentially playing a crucial role. In this study, we examined parental ramets of Focke that were subject to either a control or lead-contaminated environment (past environment), and their newborn offspring were then transplanted into control, homogeneous lead or heterogeneous lead environment (present environment). We analysed how past and present environments affect plant growth and DNA methylation in offspring. The result shown that the DNA methylation loci composition of offspring was affected by the interaction of parental environment and offspring environment, and DNA methylation levels were higher in heterogeneous environments. Moreover, our findings indicate that offspring would thrive in the heterogeneous lead environment if they did not experience lead pollution in the past, their progeny will avoid lead toxicity by reducing underground biomass allocation. However, when the parents experienced lead stress environment, their biomass allocation strategies disappeared, and they prefer to grow in favourable patches to avoid lead-contaminated patches. We concluded that the integration of historical parental exposure to lead-contaminated and current information about their offspring's environment are impacting plant phenotypes. It is possible that the stress legacy from the parents has been transmitted to their offspring ramets, and the stress legacy is at least partly based on heritable epigenetic variation. The phenotypic variation regulated by the stress legacy affects the growth performance, biomass allocation strategy, and even the behaviour of .]]>
Wed, 31 Dec 1969 19:00:00 EST
Insight into the complexity of male infertility: a multi-omics review. Podgrajsek R, Hodzic A, Stimpfel M, Kunej T, Peterlin B
Syst Biol Reprod Med (Dec 2024)

Male infertility is a reproductive disorder, accounting for 40-50% of infertility. Currently, in about 70% of infertile men, the cause remains unknown. With the introduction of novel omics and advancement in high-throughput technology, potential biomarkers are emerging. The main purpose of our work was to overview different aspects of omics approaches in association with idiopathic male infertility and highlight potential genes, transcripts, non-coding RNA, proteins, and metabolites worth further exploring. Using the Gene Ontology (GO) analysis, we aimed to compare enriched GO terms from each omics approach and determine their overlapping. A PubMed database screening for the literature published between February 2014 and June 2022 was performed using the keywords: male infertility in association with different omics approaches: genomics, epigenomics, transcriptomics, ncRNAomics, proteomics, and metabolomics. A GO enrichment analysis was performed using the Enrichr tool. We retrieved 281 global studies: 171 genomics (DNA level), 21 epigenomics (19 of methylation and two histone residue modifications), 15 transcriptomics, 31 non-coding RNA, 29 proteomics, two protein posttranslational modification, and 19 metabolomics studies. Gene ontology comparison showed that different omics approaches lead to the identification of different molecular factors and that the corresponding GO terms, obtained from different omics approaches, do not overlap to a larger extent. With the integration of novel omics levels into the research of idiopathic causes of male infertility, using multi-omic systems biology approaches, we will be closer to finding the potential biomarkers and consequently becoming aware of the entire spectrum of male infertility, their cause, prognosis, and potential treatment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection. da Silva Santos R, Pascoalino Pinheiro D, Gustavo Hirth C, Barbosa Bezerra MJ, Joyce de Lima Silva-Fernandes I, Andréa da Silva Oliveira F, Viana de Holanda Barros M, Silveira Ramos E, A Moura A, Filho OMM, Pessoa C, Miranda Furtado CL
Epigenetics (Dec 2024)

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16+ ( = 0.59) and high-risk HPV+ ( = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR ( = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.]]>
Wed, 31 Dec 1969 19:00:00 EST
Single-housing-induced islet epigenomic changes are related to polymorphisms in diabetic KK mice. Nammo T, Funahashi N, Udagawa H, Kozawa J, Nakano K, Shimizu Y, Okamura T, Kawaguchi M, Uebanso T, Nishimura W, Hiramoto M, Shimomura I, Yasuda K
Life Sci Alliance (Aug 2024)

A lack of social relationships is increasingly recognized as a type 2 diabetes (T2D) risk. To investigate the underlying mechanism, we used male KK mice, an inbred strain with spontaneous diabetes. Given the association between living alone and T2D risk in humans, we divided the non-diabetic mice into singly housed (KK-SH) and group-housed control mice. Around the onset of diabetes in KK-SH mice, we compared H3K27ac ChIP-Seq with RNA-Seq using pancreatic islets derived from each experimental group, revealing a positive correlation between single-housing-induced changes in H3K27ac and gene expression levels. In particular, single-housing-induced H3K27ac decreases revealed a significant association with islet cell functions and GWAS loci for T2D and related diseases, with significant enrichment of binding motifs for transcription factors representative of human diabetes. Although these H3K27ac regions were preferentially localized to a polymorphic genomic background, SNVs and indels did not cause sequence disruption of enriched transcription factor motifs in most of these elements. These results suggest alternative roles of genetic variants in environment-dependent epigenomic changes and provide insights into the complex mode of disease inheritance.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA. Doan TNA, Cowley JM, Phillips AL, Briffa JF, Leemaqz SY, Burton RA, Romano T, Wlodek ME, Bianco-Miotto T
Epigenetics (Dec 2024)

Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase and the imprinted genes (Cyclin-dependent kinase inhibitor 1C) and (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA ( opposite strand/antisense transcript 1). expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between and in the E20 growth restricted group (Spearman's  0.014). No correlation was observed between and expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genetic and Epigenetic Mechanisms Regulating Blood Pressure and Kidney Dysfunction. Pandey KN
Hypertension (Jul 2024)

The pioneering work of Dr Lewis K. Dahl established a relationship between kidney, salt, and high blood pressure (BP), which led to the major genetic-based experimental model of hypertension. BP, a heritable quantitative trait affected by numerous biological and environmental stimuli, is a major cause of morbidity and mortality worldwide and is considered to be a primary modifiable factor in renal, cardiovascular, and cerebrovascular diseases. Genome-wide association studies have identified monogenic and polygenic variants affecting BP in humans. Single nucleotide polymorphisms identified in genome-wide association studies have quantified the heritability of BP and the effect of genetics on hypertensive phenotype. Changes in the transcriptional program of genes may represent consequential determinants of BP, so understanding the mechanisms of the disease process has become a priority in the field. At the molecular level, the onset of hypertension is associated with reprogramming of gene expression influenced by epigenomics. This review highlights the specific genetic variants, mutations, and epigenetic factors associated with high BP and how these mechanisms affect the regulation of hypertension and kidney dysfunction.]]>
Wed, 31 Dec 1969 19:00:00 EST
Cut&tag: a powerful epigenetic tool for chromatin profiling. Fu Z, Jiang S, Sun Y, Zheng S, Zong L, Li P
Epigenetics (Dec 2024)

Analysis of transcription factors and chromatin modifications at the genome-wide level provides insights into gene regulatory processes, such as transcription, cell differentiation and cellular response. Chromatin immunoprecipitation is the most popular and powerful approach for mapping chromatin, and other enzyme-tethering techniques have recently become available for living cells. Among these, Cleavage Under Targets and Tagmentation (CUT&Tag) is a relatively novel chromatin profiling method that has rapidly gained popularity in the field of epigenetics since 2019. It has also been widely adapted to map chromatin modifications and TFs in different species, illustrating the association of these chromatin epitopes with various physiological and pathological processes. Scalable single-cell CUT&Tag can be combined with distinct platforms to distinguish cellular identity, epigenetic features and even spatial chromatin profiling. In addition, CUT&Tag has been developed as a strategy for joint profiling of the epigenome, transcriptome or proteome on the same sample. In this review, we will mainly consolidate the applications of CUT&Tag and its derivatives on different platforms, give a detailed explanation of the pros and cons of this technique as well as the potential development trends and applications in the future.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic target identification strategy based on multi-feature learning. Chen L, Gu R, Li Y, Liu H, Han W, Yan Y, Chen Y, Zhang Y, Jiang Y
J Biomol Struct Dyn (Jul 2024)

The identification of potential epigenetic targets for a known bioactive compound is essential and promising as more and more epigenetic drugs are used in cancer clinical treatment and the availability of chemogenomic data related to epigenetics increases. In this study, we introduce a novel epigenetic target identification strategy (ETI-Strategy) that integrates a multi-task graph convolutional neural network prior model and a protein-ligand interaction classification discriminating model using large-scale bioactivity data for a panel of 55 epigenetic targets. Our approach utilizes machine learning techniques to achieve an AUC value of 0.934 for the prior model and 0.830 for the discriminating model, outperforming inverse docking in predicting protein-ligand interactions. When comparing with other open-source target identification tools, it was found that only our tool was able to accurately predict all the targets corresponding to each compound. This further demonstrates the ability of our strategy to take full advantage of molecular-level information as well as protein-level information in molecular activity prediction. Our work highlights the contribution of machine learning in the identification of potential epigenetic targets and offers a novel approach for epigenetic drug discovery and development.Communicated by Ramaswamy H. Sarma.]]>
Wed, 31 Dec 1969 19:00:00 EST
Maternal adverse childhood experiences (ACEs) and offspring imprinted gene DMR methylation at birth. Vidal AC, Sosnowski DW, Marchesoni J, Grenier C, Thorp J, Murphy SK, Johnson SB, Schlief B, Hoyo C
Epigenetics (Dec 2024)

Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at /, , , and regulatory sequences using pyrosequencing. Using multivariable linear regression models, we found evidence to suggest that financial stress was associated with hypermethylation of in non-Hispanic White newborns; discrimination was associated with hypermethylation of and in Hispanic newborns, and with hypomethylation of in non-Hispanic Black newborns. We also found evidence that maternal ACEs interacted with discrimination to predict offspring altered DMR methylation, in addition to interactions between maternal ACEs score and discrimination predicting and altered methylation in non-Hispanic White newborns. However, these interactions were not statistically significant after multiple testing corrections. Findings from this study suggest that maternal ACEs, discrimination, and financial stress are associated with newborn aberrant methylation in imprinted gene regions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Methylation status of , and is associated with cardiovascular events in familial hypercholesterolemia. Silva Rodrigues Marçal ED, Borges JB, Bastos GM, Crespo Hirata TD, de Oliveira VF, Gonçalves RM, Faludi AA, Dias França JI, de Oliveira Silva DV, Malaquias VB, Luchessi AD, Silbiger VN, Nakazone MA, Carmo TS, Silva Souza DR, Sampaio MF, Crespo Hirata RD, Hirata MH
Epigenomics (Jun 2024)

Methylation of , and CpG sites was assessed in patients with familial hypercholesterolemia (FH). DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. , and methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. and methylation was higher in MD and non-MD groups than NL subjects ( < 0.05). , and methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients ( < 0.05). Differential methylation of , and is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted lncRNA KCNQ1OT1 regulates CDKN1C expression through promoter binding and chromatin folding in pigs. Zhou Y, Yu H, Zhang D, Wang Z, Li Q, An X, Zhang S, Li Z
Gene (Sep 2024)

Long noncoding RNAs (lncRNAs) are implicated in a number of regulatory functions in eukaryotic genomes. In humans, KCNQ1OT1 is a 91 kb imprinted lncRNA that inhibits multiple surrounding genes in cis. Among them, CDKN1C is closely related to KCNQ1OT1 and is involved in multiple epigenetic disorders. Here, we found that pigs also had a relatively conserved paternal allele expressing KCNQ1OT1 and had a shorter 5' end (∼27 kb) compared to human KCNQ1OT1. Knockdown of KCNQ1OT1 using antisense oligonucleotides (ASO) showed that upregulation of CDKN1C expression in pigs. However, porcine KCNQ1OT1 did not affect the DNA methylation status of the CpG islands in the promoters of KCNQ1OT1 and CDKN1C. Inhibition of DNA methyltransferase using Decitabine treatment resulted in a significant increase in both KCNQ1OT1 and CDKN1C expression, suggesting that the regulation between KCNQ1OT1 and CDKN1C may not be dependent on RNA interference. Further use of chromosome conformation capture and reverse transcription-associated trap detection in the region where CDKN1C was located revealed that KCNQ1OT1 bound to the CDKN1C promoter and affected chromosome folding. Phenotypically, inhibition of KCNQ1OT1 at the cumulus-oocyte complex promoted cumulus cell transformation, and to upregulated the expression of ALPL at the early stage of osteogenic differentiation of porcine bone marrow mesenchymal stem cells. Our results confirm that the expression of KCNQ1OT1 imprinting in pigs as well as porcine KCNQ1OT1 regulates the expression of CDKN1C through direct promoter binding and chromatin folding alteration. And this regulatory mechanism played an important role in cell differentiation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma. El Zarif T, Semaan K, Eid M, Seo JH, Garinet S, Davidsohn MP, Sahgal P, Fortunato B, Canniff J, Nassar AH, Abou Alaiwi S, Bakouny Z, Lakshminarayanan G, Savignano H, Lyons K, Matar S, Ali A, Saad E, Saliby RM, Cordeiro P, Zhang Z, El Ahmar N, Laimon YN, Labaki C, Shah V, Freeman D, O'Toole J, Lee GM, Hwang J, Pomerantz M, Signoretti S, Van Allen EM, Xie W, Berchuck JE, Viswanathan SR, Braun DA, Choueiri TK, Freedman ML, Baca SC
Cell Rep (Jun 2024)

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.]]>
Wed, 31 Dec 1969 19:00:00 EST