Epigenetics & Chromatin最新文献

{"title":"Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression.","authors":"Annalisa Izzo, Ipek Akol, Alejandro Villarreal, Shannon Lebel, Marta Garcia-Miralles, Arquimedes Cheffer, Patrick Bovio, Stefanie Heidrich, Tanja Vogel","doi":"10.1186/s13072-023-00511-9","DOIUrl":"10.1186/s13072-023-00511-9","url":null,"abstract":"<p><strong>Background: </strong>NPM1 is a phosphoprotein highly abundant in the nucleolus. However, additional nuclear functions have been attributed to NPM1, probably through interaction with other nuclear factors. DOT1L is one interaction partner of NPM1 that catalyzes methylation of histone H3 at lysine 79 (H3K79). DOT1L, playing functional roles in several biological processes, is known for its capability to organize and regulate chromatin. For example, DOT1L modulates DNA repeats expression within peri-nucleolar heterochromatin. NPM1 also affects peri-nucleolar heterochromatin spatial organization. However, it is unclear as of yet whether NPM1 and DOT1L functionally synergize to preserve nucleoli organization and genome stability, and generally, which molecular mechanisms would be involved.</p><p><strong>Results: </strong>We characterized the nuclear function of NPM1 on peri-nucleolar heterochromatin organization. We show that (i) monomeric NPM1 interacts preferentially with DOT1L in the nucleus; (ii) NPM1 acts in concert with DOT1L to maintain each other's protein homeostasis; (iii) NPM1 depletion results in H3K79me2 upregulation and differential enrichment at chromatin binding genes including Ezh2; (iv) NPM1 and DOT1L modulate DNA repeats expression and peri-nucleolar heterochromatin organization via epigenetic mechanisms dependent on H3K27me3.</p><p><strong>Conclusions: </strong>Our findings give insights into molecular mechanisms employed by NPM1 and DOT1L to regulate heterochromatin activity and structural organization around the nucleoli and shed light on one aspect of the complex role of both proteins in chromatin dynamics.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"36"},"PeriodicalIF":3.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone crotonylation of peripheral blood mononuclear cells is a potential biomarker for diagnosis of colorectal cancer.","authors":"Jia-Yi Hou, Ning Li, Jie Wang, Li-Juan Gao, Jia-Song Chang, Ji-Min Cao","doi":"10.1186/s13072-023-00509-3","DOIUrl":"10.1186/s13072-023-00509-3","url":null,"abstract":"<p><strong>Background: </strong>Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC).</p><p><strong>Results: </strong>Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays.</p><p><strong>Conclusions: </strong>The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"35"},"PeriodicalIF":3.9,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating disease-associated mechanisms triggered by pollutants via the epigenetic landscape using large-scale ChIP-Seq data.","authors":"Zhaonan Zou, Yuka Yoshimura, Yoshihiro Yamanishi, Shinya Oki","doi":"10.1186/s13072-023-00510-w","DOIUrl":"10.1186/s13072-023-00510-w","url":null,"abstract":"<p><strong>Background: </strong>Despite well-documented effects on human health, the action modes of environmental pollutants are incompletely understood. Although transcriptome-based approaches are widely used to predict associations between chemicals and disorders, the molecular cues regulating pollutant-derived gene expression changes remain unclear. Therefore, we developed a data-mining approach, termed \"DAR-ChIPEA,\" to identify transcription factors (TFs) playing pivotal roles in the action modes of pollutants.</p><p><strong>Methods: </strong>Large-scale public ChIP-Seq data (human, n = 15,155; mouse, n = 13,156) were used to predict TFs that are enriched in the pollutant-induced differentially accessible genomic regions (DARs) obtained from epigenome analyses (ATAC-Seq). The resultant pollutant-TF matrices were then cross-referenced to a repository of TF-disorder associations to account for pollutant modes of action. We subsequently evaluated the performance of the proposed method using a chemical perturbation data set to compare the outputs of the DAR-ChIPEA and our previously developed differentially expressed gene (DEG)-ChIPEA methods using pollutant-induced DEGs as input. We then adopted the proposed method to predict disease-associated mechanisms triggered by pollutants.</p><p><strong>Results: </strong>The proposed approach outperformed other methods using the area under the receiver operating characteristic curve score. The mean score of the proposed DAR-ChIPEA was significantly higher than that of our previously described DEG-ChIPEA (0.7287 vs. 0.7060; Q = 5.278 × 10^-42; two-tailed Wilcoxon rank-sum test). The proposed approach further predicted TF-driven modes of action upon pollutant exposure, indicating that (1) TFs regulating Th1/2 cell homeostasis are integral in the pathophysiology of tributyltin-induced allergic disorders; (2) fine particulates (PM_2.5) inhibit the binding of C/EBPs, Rela, and Spi1 to the genome, thereby perturbing normal blood cell differentiation and leading to immune dysfunction; and (3) lead induces fatty liver by disrupting the normal regulation of lipid metabolism by altering hepatic circadian rhythms.</p><p><strong>Conclusions: </strong>Highlighting genome-wide chromatin change upon pollutant exposure to elucidate the epigenetic landscape of pollutant responses outperformed our previously described method that focuses on gene-adjacent domains only. Our approach has the potential to reveal pivotal TFs that mediate deleterious effects of pollutants, thereby facilitating the development of strategies to mitigate damage from environmental pollution.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"34"},"PeriodicalIF":3.9,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.","authors":"Jun Wang, Yanqin Niu, Ming Yang, Lirong Shu, Hongxian Wang, Xiaoqian Wu, Yaqin He, Peng Chen, Guocheng Zhong, Zhixiong Tang, Shasha Zhang, Qianwen Guo, Yun Wang, Li Yu, Deming Gou","doi":"10.1186/s13072-023-00508-4","DOIUrl":"10.1186/s13072-023-00508-4","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear.</p><p><strong>Methods: </strong>Improved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 49 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hypermethylated regions as diagnostic markers for breast cancer was evaluated.</p><p><strong>Results: </strong>Mean size of cfDNA fragments (100-220 bp) mapped to hypomethylated regions decreased more in patients with breast cancer (4.60 bp, 172.33 to 167.73 bp) than in healthy individuals (2.87 bp, 174.54 to 171.67 bp). Furthermore, proportion of short cfDNA fragments (100-150 bp) in hypomethylated regions when compared with it in hypermethylated regions was found to increase more in patients with breast cancer in two independent discovery cohort. The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for breast cancer diagnosis in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity).</p><p><strong>Conclusion: </strong>We identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"33"},"PeriodicalIF":3.9,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-effects of m6A and chromatin accessibility dynamics in the regulation of cardiomyocyte differentiation.","authors":"Xue-Hong Liu, Zhun Liu, Ze-Hui Ren, Hong-Xuan Chen, Ying Zhang, Zhang Zhang, Nan Cao, Guan-Zheng Luo","doi":"10.1186/s13072-023-00506-6","DOIUrl":"10.1186/s13072-023-00506-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood.</p><p><strong>Results: </strong>We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts.</p><p><strong>Conclusion: </strong>Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"32"},"PeriodicalIF":3.9,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers.","authors":"Musa Idris, Louis Coussement, Maria M Alves, Tim De Meyer, Veerle Melotte","doi":"10.1186/s13072-023-00505-7","DOIUrl":"10.1186/s13072-023-00505-7","url":null,"abstract":"<p><strong>Background: </strong>DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA).</p><p><strong>Results: </strong>All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature.</p><p><strong>Conclusion: </strong>Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"31"},"PeriodicalIF":3.9,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etiology of super-enhancer reprogramming and activation in cancer.","authors":"Royce W Zhou,&nbsp;Ramon E Parsons","doi":"10.1186/s13072-023-00502-w","DOIUrl":"https://doi.org/10.1186/s13072-023-00502-w","url":null,"abstract":"<p><p>Super-enhancers are large, densely concentrated swaths of enhancers that regulate genes critical for cell identity. Tumorigenesis is accompanied by changes in the super-enhancer landscape. These aberrant super-enhancers commonly form to activate proto-oncogenes, or other genes upon which cancer cells depend, that initiate tumorigenesis, promote tumor proliferation, and increase the fitness of cancer cells to survive in the tumor microenvironment. These include well-recognized master regulators of proliferation in the setting of cancer, such as the transcription factor MYC which is under the control of numerous super-enhancers gained in cancer compared to normal tissues. This Review will cover the expanding cell-intrinsic and cell-extrinsic etiology of these super-enhancer changes in cancer, including somatic mutations, copy number variation, fusion events, extrachromosomal DNA, and 3D chromatin architecture, as well as those activated by inflammation, extra-cellular signaling, and the tumor microenvironment.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"29"},"PeriodicalIF":3.9,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in the hepatocyte epigenetic landscape in steatosis.","authors":"Ranjan Kumar Maji,&nbsp;Beate Czepukojc,&nbsp;Michael Scherer,&nbsp;Sascha Tierling,&nbsp;Cristina Cadenas,&nbsp;Kathrin Gianmoena,&nbsp;Nina Gasparoni,&nbsp;Karl Nordström,&nbsp;Gilles Gasparoni,&nbsp;Stephan Laggai,&nbsp;Xinyi Yang,&nbsp;Anupam Sinha,&nbsp;Peter Ebert,&nbsp;Maren Falk-Paulsen,&nbsp;Sarah Kinkley,&nbsp;Jessica Hoppstädter,&nbsp;Ho-Ryun Chung,&nbsp;Philip Rosenstiel,&nbsp;Jan G Hengstler,&nbsp;Jörn Walter,&nbsp;Marcel H Schulz,&nbsp;Sonja M Kessler,&nbsp;Alexandra K Kiemer","doi":"10.1186/s13072-023-00504-8","DOIUrl":"https://doi.org/10.1186/s13072-023-00504-8","url":null,"abstract":"<p><p>Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"30"},"PeriodicalIF":3.9,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Dmnt1 during spermatogenesis of the insect Oncopeltus fasciatus.","authors":"Christopher B Cunningham,&nbsp;Emily A Shelby,&nbsp;Elizabeth C McKinney,&nbsp;Robert J Schmitz,&nbsp;Allen J Moore,&nbsp;Patricia J Moore","doi":"10.1186/s13072-023-00496-5","DOIUrl":"https://doi.org/10.1186/s13072-023-00496-5","url":null,"abstract":"<p><strong>Background: </strong>The function of DNA methyltransferase genes of insects is a puzzle, because an association between gene expression and methylation is not universal for insects. If the genes normally involved in cytosine methylation are not influencing gene expression, what might be their role? We previously demonstrated that gametogenesis of Oncopeltus fasciatus is interrupted at meiosis following knockdown of DNA methyltransferase 1 (Dnmt1) and this is unrelated to changes in levels of cytosine methylation. Here, using transcriptomics, we tested the hypothesis that Dmnt1 is a part of the meiotic gene pathway. Testes, which almost exclusively contain gametes at varying stages of development, were sampled at 7 days and 14 days following knockdown of Dmnt1 using RNAi.</p><p><strong>Results: </strong>Using microscopy, we found actively dividing spermatocysts were reduced at both timepoints. However, as with other studies, we saw Dnmt1 knockdown resulted in condensed nuclei after mitosis-meiosis transition, and then cellular arrest. We found limited support for a functional role for Dnmt1 in our predicted cell cycle and meiotic pathways. An examination of a priori Gene Ontology terms showed no enrichment for meiosis. We then used the full data set to reveal further candidate pathways influenced by Dnmt1 for further hypotheses. Very few genes were differentially expressed at 7 days, but nearly half of all transcribed genes were differentially expressed at 14 days. We found no strong candidate pathways for how Dnmt1 knockdown was achieving its effect through Gene Ontology term overrepresentation analysis.</p><p><strong>Conclusions: </strong>We, therefore, suggest that Dmnt1 plays a role in chromosome dynamics based on our observations of condensed nuclei and cellular arrest with no specific molecular pathways disrupted.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"28"},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live-cell imaging of chromatin contacts opens a new window into chromatin dynamics.","authors":"Jente van Staalduinen, Thomas van Staveren, Frank Grosveld, Kerstin S Wendt","doi":"10.1186/s13072-023-00503-9","DOIUrl":"10.1186/s13072-023-00503-9","url":null,"abstract":"<p><p>Our understanding of the organization of the chromatin fiber within the cell nucleus has made great progress in the last few years. High-resolution techniques based on next-generation sequencing as well as optical imaging that can investigate chromatin conformations down to the single cell level have revealed that chromatin structure is highly heterogeneous at the level of the individual allele. While TAD boundaries and enhancer-promoter pairs emerge as hotspots of 3D proximity, the spatiotemporal dynamics of these different types of chromatin contacts remain largely unexplored. Investigation of chromatin contacts in live single cells is necessary to close this knowledge gap and further enhance the current models of 3D genome organization and enhancer-promoter communication. In this review, we first discuss the potential of single locus labeling to study architectural and enhancer-promoter contacts and provide an overview of the available single locus labeling techniques such as FROS, TALE, CRISPR-dCas9 and ANCHOR, and discuss the latest developments and applications of these systems.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"27"},"PeriodicalIF":4.2,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9709861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}