'; ?> 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 Wed, 27 Mar 2024 21:54:49 EDT Wed, 27 Mar 2024 21:54:49 EDT jirtle@radonc.duke.edu james001@jirtle.com Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study. Pina C
Philos Trans R Soc Lond B Biol Sci (Apr 2024)

Transcriptional noise is proposed to participate in cell fate changes, but contributions to mammalian cell differentiation systems, including cancer, remain associative. Cancer evolution is driven by genetic variability, with modulatory or contributory participation of epigenetic variants. Accumulation of epigenetic variants enhances transcriptional noise, which can facilitate cancer cell fate transitions. Acute myeloid leukaemia (AML) is an aggressive cancer with strong epigenetic dependencies, characterized by blocked differentiation. It constitutes an attractive model to probe links between transcriptional noise and malignant cell fate regulation. Gcn5/KAT2A is a classical epigenetic transcriptional noise regulator. Its loss increases transcriptional noise and modifies cell fates in stem and AML cells. By reviewing the analysis of KAT2A-depleted pre-leukaemia and leukaemia models, I discuss that the net result of transcriptional noise is diversification of cell fates secondary to alternative transcriptional programmes. Cellular diversification can enable or hinder AML progression, respectively, by differentiation of cell types responsive to mutations, or by maladaptation of leukaemia stem cells. KAT2A-dependent noise-responsive genes participate in ribosome biogenesis and KAT2A loss destabilizes translational activity. I discuss putative contributions of perturbed translation to AML biology, and propose KAT2A loss as a model for mechanistic integration of transcriptional and translational control of noise and fate decisions. This article is part of a discussion meeting issue 'Causes and consequences of stochastic processes in development and disease'.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-wide 5'-C-phosphate-G-3' methylation patterns reveal the effect of heat stress on the altered semen quality in Bubalus bubalis. Kumar G, Gurao A, Vasisth R, Chitkara M, Singh R, Ranganatha Sriranga K, Shivanand Dige M, Mukesh M, Singh P, Singh Kataria R
Gene (May 2024)

Semen production and quality are closely correlated with different environmental factors in bovines, particularly for the buffalo (Bubalus bubalis) bulls reared under tropical and sub-tropical conditions. Factors including DNA methylation patterns, an intricate process in sperm cells, have an impact on the production of quality semen in buffalo bulls under abiotic stress conditions. The present study was conducted to identify DNA methylome signatures for semen quality in Murrah buffalo bulls, acclaimed as a major dairy breed globally, under summer heat stress. Based on semen quality parameters that significantly varied between the two groups over the seasons, the breeding bulls were classified into seasonally affected (SA = 6) and seasonally non-affected (SNA = 6) categories. DNA was isolated from purified sperm cells and sequenced using the RRBS (Reduced Representation Bisulfite Sequencing) technique for genome-wide methylome data generation. During the hot summer months, the physiological parameters such as scrotal surface temperature, rectal temperature, and respiration rate for both the SA and SNA bulls were significantly higher in the afternoon than in the morning. Whereas, the global CpG% of SA bulls was positively correlated with the afternoon's scrotal surface and rectal temperature. The RRBS results conveyed differentially methylated cytosines in the promoter region of the genes encoding the channels responsible for Ca exchange, NPTN, Ca activated chloride channels, ANO1, and a few structure-related units such as septins (SEPT4 and SEPT6), SPATA, etc. Additionally, the hypermethylated set of genes in SA was significantly enriched for pathways such as the FOXO signaling pathway and oocyte meiosis. The methylation patterns suggest promoter methylation in the genes regulating the sperm structure as well as surface transporters, which could contribute to the reduced semen quality in the Murrah buffalo bulls during the season-related heat stress.]]>
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
Transgenerational Epigenetic Inheritance of Cardiovascular Diseases: A Network Medicine Perspective. Benincasa G, Napoli C, DeMeo DL
Matern Child Health J (Apr 2024)

The ability to identify early epigenetic signatures underlying the inheritance of cardiovascular risk, including trans- and intergenerational effects, may help to stratify people before cardiac symptoms occur.]]>
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
METTL1 facilitates ameloblastoma invasive growth via MAPK signaling pathway. Wang Y, Xiong G, Cai W, Tao Q
Gene (May 2024)

Ameloblastoma (AM), a common odontogenic epithelial tumor, exhibits aggressive growth due to incomplete encapsulation within the jawbone. Postoperative recurrence is a significant concern, closely associated with its invasive nature. We investigate the role of tRNA N-7 methylguanosine (mG) modification mediated by Methyltransferase-like 1 (METTL1) in AM's invasive growth and prognosis.]]>
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
Inheritance of epigenetic transcriptional memory. Ge T, Brickner JH
Curr Opin Genet Dev (Apr 2024)

Epigenetic memory allows organisms to stably alter their transcriptional program in response to developmental or environmental stimuli. Such transcriptional programs are mediated by heritable regulation of the function of enhancers and promoters. Memory involves read-write systems that enable self-propagation and mitotic inheritance of cis-acting epigenetic marks to induce stable changes in transcription. Also, in response to environmental cues, cells can induce epigenetic transcriptional memory to poise inducible genes for faster induction in the future. Here, we discuss modes of epigenetic inheritance and the molecular basis of epigenetic transcriptional memory.]]>
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
DUX4-induced HSATII transcription causes KDM2A/B-PRC1 nuclear foci and impairs DNA damage response. Arends T, Tsuchida H, Adeyemi RO, Tapscott SJ
J Cell Biol (May 2024)

Polycomb repressive complexes regulate developmental gene programs, promote DNA damage repair, and mediate pericentromeric satellite repeat repression. Expression of pericentromeric satellite repeats has been implicated in several cancers and diseases, including facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4-mediated transcription of HSATII regions causes nuclear foci formation of KDM2A/B-PRC1 complexes, resulting in a global loss of PRC1-mediated monoubiquitination of histone H2A. Loss of PRC1-ubiquitin signaling severely impacts DNA damage response. Our data implicate DUX4-activation of HSATII and sequestration of KDM2A/B-PRC1 complexes as a mechanism of regulating epigenetic and DNA repair pathways.]]>
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
Conserved and divergent features of trophoblast stem cells. Sah N, Soncin F
J Mol Endocrinol (May 2024)

Trophoblast stem cells (TSCs) are a proliferative multipotent population derived from the trophectoderm of the blastocyst, which will give rise to all the functional cell types of the trophoblast compartment of the placenta. The isolation and culture of TSCs in vitro represent a robust model to study mechanisms of trophoblast differentiation into mature cells both in successful and diseased pregnancy. Despite the highly conserved functions of the placenta, there is extreme variability in placental morphology, fetal-maternal interface, and development among eutherian mammals. This review aims to summarize the establishment and maintenance of TSCs in mammals such as primates, including human, rodents, and nontraditional animal models with a primary emphasis on epigenetic regulation of their origin while defining gaps in the current literature and areas of further development. FGF signaling is critical for mouse TSCs but dispensable for derivation of TSCs in other species. Human, simian, and bovine TSCs have much more complicated requirements of signaling pathways including activation of WNT and inhibition of TGFβ cascades. Epigenetic features such as DNA and histone methylation as well as histone acetylation are dynamic during development and are expressed in cell- and gestational age-specific pattern in placental trophoblasts. While TSCs from different species seem to recapitulate some select epigenomic features, there is a limitation in the comprehensive understanding of TSCs and how well TSCs retain placental epigenetic marks. Therefore, future studies should be directed at investigating epigenomic features of global and placental-specific gene expression in primary trophoblasts and TSCs.]]>
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
A preliminary investigation of epigenome-wide DNA methylation and temperament during infancy. Leri J, Liu J, Kelly M, Kertes DA
Dev Psychobiol (Apr 2024)

This study provides preliminary evidence for an epigenetic architecture of infant temperament. At 12 months of age, blood was collected and assayed for DNA methylation and maternally reported infant temperament was assessed using the Infant Behavior Questionnaire in 67 mother-infant dyads. Epigenome-wide analyses showed that the higher order temperament dimensions Surgency and Negative Affect were associated with DNA methylation. The epigenetic signatures of Surgency and Negative Affect were situated at genes involved in synaptic signaling and plasticity. Although replication is required, these results are consistent with a biologically based model of temperament, create new avenues for hypothesis-driven research into epigenetic pathways that underlie individual differences in temperament, and demonstrate that infant temperament has a widespread epigenetic signature in the methylome.]]>
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
Differential methylation patterns from clusters associated with glucose metabolism: evidence from a Shanghai twin study. Feng J, Zhu Z, Zhou R, Liu H, Hu Z, Wu F, Wang H, Yue J, Zhou T, Yang L, Wu F
Epigenomics (Apr 2024)

To assess the associations between genome-wide DNA methylation (DNAm) and glucose metabolism among a Chinese population, in particular the multisite correlation. Epigenome-wide associations with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were analyzed among 100 Shanghai monozygotic (MZ) twin pairs using the Infinium HumanMethylationEPIC v2.0 BeadChip. We conducted a Pearson's correlation test, hierarchical cluster and pairwise analysis to examine the differential methylation patterns from clusters. Cg01358804 () was identified as the most significant site associated with FPG and HbA1c. Two clusters with hypermethylated and hypomethylated patterns were observed for both FPG and HbA1c. Differential methylation patterns from clusters may provide new clues for epigenetic changes and biological mechanisms in glucose metabolism.]]>
Wed, 31 Dec 1969 19:00:00 EST
A review of the role of epigenetic studies for intramuscular fat deposition in beef cattle. Kuraz Abebe B, Wang J, Guo J, Wang H, Li A, Zan L
Gene (May 2024)

Intramuscular fat (IMF) deposition profoundly influences meat quality and economic value in beef cattle production. Meanwhile, contemporary developments in epigenetics have opened new outlooks for understanding the molecular basics of IMF regulation, and it has become a key area of research for world scholars. Therefore, the aim of this paper was to provide insight and synthesis into the intricate relationship between epigenetic mechanisms and IMF deposition in beef cattle. The methodology involves a thorough analysis of existing literature, including pertinent books, academic journals, and online resources, to provide a comprehensive overview of the role of epigenetic studies in IMF deposition in beef cattle. This review summarizes the contemporary studies in epigenetic mechanisms in IMF regulation, high-resolution epigenomic mapping, single-cell epigenomics, multi-omics integration, epigenome editing approaches, longitudinal studies in cattle growth, environmental epigenetics, machine learning in epigenetics, ethical and regulatory considerations, and translation to industry practices from perspectives of IMF deposition in beef cattle. Moreover, this paper highlights DNA methylation, histone modifications, acetylation, phosphorylation, ubiquitylation, non-coding RNAs, DNA hydroxymethylation, epigenetic readers, writers, and erasers, chromatin immunoprecipitation followed by sequencing, whole genome bisulfite sequencing, epigenome-wide association studies, and their profound impact on the expression of crucial genes governing adipogenesis and lipid metabolism. Nutrition and stress also have significant influences on epigenetic modifications and IMF deposition. The key findings underscore the pivotal role of epigenetic studies in understanding and enhancing IMF deposition in beef cattle, with implications for precision livestock farming and ethical livestock management. In conclusion, this review highlights the crucial significance of epigenetic pathways and environmental factors in affecting IMF deposition in beef cattle, providing insightful information for improving the economics and meat quality of cattle production.]]>
Wed, 31 Dec 1969 19:00:00 EST
Tunable DNMT1 degradation reveals DNMT1/DNMT3B synergy in DNA methylation and genome organization. Scelfo A, Barra V, Abdennur N, Spracklin G, Busato F, Salinas-Luypaert C, Bonaiti E, Velasco G, Bonhomme F, Chipont A, Tijhuis AE, Spierings DCJ, Guérin C, Arimondo P, Francastel C, Foijer F, Tost J, Mirny L, Fachinetti D
J Cell Biol (Apr 2024)

DNA methylation (DNAme) is a key epigenetic mark that regulates critical biological processes maintaining overall genome stability. Given its pleiotropic function, studies of DNAme dynamics are crucial, but currently available tools to interfere with DNAme have limitations and major cytotoxic side effects. Here, we present cell models that allow inducible and reversible DNAme modulation through DNMT1 depletion. By dynamically assessing whole genome and locus-specific effects of induced passive demethylation through cell divisions, we reveal a cooperative activity between DNMT1 and DNMT3B, but not of DNMT3A, to maintain and control DNAme. We show that gradual loss of DNAme is accompanied by progressive and reversible changes in heterochromatin, compartmentalization, and peripheral localization. DNA methylation loss coincides with a gradual reduction of cell fitness due to G1 arrest, with minor levels of mitotic failure. Altogether, this system allows DNMTs and DNA methylation studies with fine temporal resolution, which may help to reveal the etiologic link between DNAme dysfunction and human disease.]]>
Wed, 31 Dec 1969 19:00:00 EST