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
{"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":null,"pages":null},"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}
Xue-Hong Liu, Zhun Liu, Ze-Hui Ren, Hong-Xuan Chen, Ying Zhang, Zhang Zhang, Nan Cao, Guan-Zheng Luo
{"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":null,"pages":null},"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}
Musa Idris, Louis Coussement, Maria M Alves, Tim De Meyer, Veerle Melotte
{"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":null,"pages":null},"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, 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":null,"pages":null},"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}
Ranjan Kumar Maji, Beate Czepukojc, Michael Scherer, Sascha Tierling, Cristina Cadenas, Kathrin Gianmoena, Nina Gasparoni, Karl Nordström, Gilles Gasparoni, Stephan Laggai, Xinyi Yang, Anupam Sinha, Peter Ebert, Maren Falk-Paulsen, Sarah Kinkley, Jessica Hoppstädter, Ho-Ryun Chung, Philip Rosenstiel, Jan G Hengstler, Jörn Walter, Marcel H Schulz, Sonja M Kessler, Alexandra K Kiemer
{"title":"Alterations in the hepatocyte epigenetic landscape in steatosis.","authors":"Ranjan Kumar Maji, Beate Czepukojc, Michael Scherer, Sascha Tierling, Cristina Cadenas, Kathrin Gianmoena, Nina Gasparoni, Karl Nordström, Gilles Gasparoni, Stephan Laggai, Xinyi Yang, Anupam Sinha, Peter Ebert, Maren Falk-Paulsen, Sarah Kinkley, Jessica Hoppstädter, Ho-Ryun Chung, Philip Rosenstiel, Jan G Hengstler, Jörn Walter, Marcel H Schulz, Sonja M Kessler, 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":null,"pages":null},"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}
Christopher B Cunningham, Emily A Shelby, Elizabeth C McKinney, Robert J Schmitz, Allen J Moore, Patricia J Moore
{"title":"The role of Dmnt1 during spermatogenesis of the insect Oncopeltus fasciatus.","authors":"Christopher B Cunningham, Emily A Shelby, Elizabeth C McKinney, Robert J Schmitz, Allen J Moore, 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":null,"pages":null},"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}
Jente van Staalduinen, Thomas van Staveren, Frank Grosveld, Kerstin S Wendt
{"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":null,"pages":null},"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}
Alena Svobodová Kovaříková, Lenka Stixová, Aleš Kovařík, Eva Bártová
{"title":"PARP-dependent and NAT10-independent acetylation of N4-cytidine in RNA appears in UV-damaged chromatin.","authors":"Alena Svobodová Kovaříková, Lenka Stixová, Aleš Kovařík, Eva Bártová","doi":"10.1186/s13072-023-00501-x","DOIUrl":"https://doi.org/10.1186/s13072-023-00501-x","url":null,"abstract":"<p><p>RNA modifications have been known for many years, but their function has not been fully elucidated yet. For instance, the regulatory role of acetylation on N4-cytidine (ac4C) in RNA can be explored not only in terms of RNA stability and mRNA translation but also in DNA repair. Here, we observe a high level of ac4C RNA at DNA lesions in interphase cells and irradiated cells in telophase. Ac4C RNA appears in the damaged genome from 2 to 45 min after microirradiation. However, RNA cytidine acetyltransferase NAT10 did not accumulate to damaged sites, and NAT10 depletion did not affect the pronounced recruitment of ac4C RNA to DNA lesions. This process was not dependent on the G1, S, and G2 cell cycle phases. In addition, we observed that the PARP inhibitor, olaparib, prevents the recruitment of ac4C RNA to damaged chromatin. Our data imply that the acetylation of N4-cytidine, especially in small RNAs, has an important role in mediating DNA damage repair. Ac4C RNA likely causes de-condensation of chromatin in the vicinity of DNA lesions, making it accessible for other DNA repair factors involved in the DNA damage response. Alternatively, RNA modifications, including ac4C, could be direct markers of damaged RNAs.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10010974","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}
Alla Krasikova, Tatiana Kulikova, Juan Sebastian Rodriguez Ramos, Antonina Maslova
{"title":"Assignment of the somatic A/B compartments to chromatin domains in giant transcriptionally active lampbrush chromosomes.","authors":"Alla Krasikova, Tatiana Kulikova, Juan Sebastian Rodriguez Ramos, Antonina Maslova","doi":"10.1186/s13072-023-00499-2","DOIUrl":"https://doi.org/10.1186/s13072-023-00499-2","url":null,"abstract":"<p><strong>Background: </strong>The three-dimensional configuration of the eukaryotic genome is an emerging area of research. Chromosome conformation capture outlined genome segregation into large scale A and B compartments corresponding mainly to transcriptionally active and repressive chromatin. It remains unknown how the compartmentalization of the genome changes in growing oocytes of animals with hypertranscriptional type of oogenesis. Such oocytes are characterized by highly elongated chromosomes, called lampbrush chromosomes, which acquire a typical chromomere-loop appearance, representing one of the classical model systems for exploring the structural and functional organization of chromatin domains.</p><p><strong>Results: </strong>Here, we compared the distribution of A/B compartments in chicken somatic cells with chromatin domains in lampbrush chromosomes. We found that in lampbrush chromosomes, the extended chromatin domains, restricted by compartment boundaries in somatic cells, disintegrate into individual chromomeres. Next, we performed FISH-mapping of the genomic loci, which belong to A or B chromatin compartments as well as to A/B compartment transition regions in embryonic fibroblasts on isolated lampbrush chromosomes. We found, that in chicken lampbrush chromosomes, clusters of dense compact chromomeres bearing short lateral loops and enriched with repressive epigenetic modifications generally correspond to constitutive B compartments in somatic cells. A compartments align with lampbrush chromosome segments with smaller, less compact chromomeres, longer lateral loops, and a higher transcriptional status. Clusters of small loose chromomeres with relatively long lateral loops show no obvious correspondence with either A or B compartment identity. Some genes belonging to facultative B (sub-) compartments can be tissue-specifically transcribed during oogenesis, forming distinct lateral loops.</p><p><strong>Conclusions: </strong>Here, we established a correspondence between the A/B compartments in somatic interphase nucleus and chromatin segments in giant lampbrush chromosomes from diplotene stage oocytes. The chromomere-loop structure of the genomic regions corresponding to interphase A and B compartments reveals the difference in how they are organized at the level of chromatin domains. The results obtained also suggest that gene-poor regions tend to be packed into chromomeres.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028209","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}
Ashley B Reers, Rodriel Bautista, James McLellan, Beatriz Morales, Rolando Garza, Sebastiaan Bol, Kirsten K Hanson, Evelien M Bunnik
{"title":"Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.","authors":"Ashley B Reers, Rodriel Bautista, James McLellan, Beatriz Morales, Rolando Garza, Sebastiaan Bol, Kirsten K Hanson, Evelien M Bunnik","doi":"10.1186/s13072-023-00500-y","DOIUrl":"10.1186/s13072-023-00500-y","url":null,"abstract":"<p><p>Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq on P. falciparum blood stage schizonts, merozoites, and rings, as well as P. berghei liver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816933","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}