{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:26:09Z","timestamp":1780467969447,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31972694"],"award-info":[{"award-number":["31972694"]}]},{"name":"National Natural Science Foundation of China","award":["1090064"],"award-info":[{"award-number":["1090064"]}]},{"name":"National Natural Science Foundation of China","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"name":"Precision Animal Husbandry Discipline Group Construction Project of Hebei Agricultural University","award":["31972694"],"award-info":[{"award-number":["31972694"]}]},{"name":"Precision Animal Husbandry Discipline Group Construction Project of Hebei Agricultural University","award":["1090064"],"award-info":[{"award-number":["1090064"]}]},{"name":"Precision Animal Husbandry Discipline Group Construction Project of Hebei Agricultural University","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"name":"third batch of the Top Young Talent Program in Hebei Province","award":["31972694"],"award-info":[{"award-number":["31972694"]}]},{"name":"third batch of the Top Young Talent Program in Hebei Province","award":["1090064"],"award-info":[{"award-number":["1090064"]}]},{"name":"third batch of the Top Young Talent Program in Hebei Province","award":["2018"],"award-info":[{"award-number":["2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mast cells can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) via mannose receptors (MRs) to produce differentially expressed cytokines. The regulatory role of chromatin accessibility in this process is unclear. Bone marrow-derived mast cells (BMMCs) were cultured, and an assay of transposase-accessible chromatin sequencing (ATAC-seq) was applied to demonstrate the regulation of chromatin accessibility in response to the BMMCs\u2019 recognition of FMDV-VLPs. A pathway enrichment analysis showed that peaks associated with the nuclear factor-\u03baB (NF-\u03baB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), and other signaling pathways, especially the NF-\u03baB pathway, were involved in the BMMCs\u2019 recognition of VLPs. Moreover, transcription factors including SP1, NRF1, AP1, GATA3, microphthalmia-associated transcription factor (MITF), and NF-\u03baB-p65 may bind to the motifs with altered chromatin accessibility to regulate gene transcription. Furthermore, the expression of NF-\u03baB, interleukin (IL)-9, tumor necrosis factor (TNF)-\u03b1, and interferon (IFN)-\u03b3 in the BMMCs of the VLP group increased compared with that of the BMMCs in the control group, whereas the expression of IL-10 did not differ significantly between groups. After inhibiting the MRs, the expression of NF-\u03baB, IL-9, TNF-\u03b1, and IFN-\u03b3 decreased significantly, whereas the expression of IL-10 increased. The expression of MAPK and IL-6 showed no significant change after MR inhibition. This study demonstrated that MRs expressed on BMMCs can affect the NF-\u03baB pathway by changing chromatin accessibility to regulate the transcription of specific cytokines, ultimately leading to the differential expression of cytokines. These data provide a theoretical basis and new ideas for the development of a novel vaccine for FMD.<\/jats:p>","DOI":"10.3390\/ijms242317044","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T10:39:48Z","timestamp":1701427188000},"page":"17044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of Chromatin Accessibility Changes Induced by BMMC Recognition of Foot-and-Mouth Disease Virus-like Particles through ATAC-seq"],"prefix":"10.3390","volume":"24","author":[{"given":"Weijian","family":"Han","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manxin","family":"An","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-151X","authenticated-orcid":false,"given":"Limin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.coviro.2018.02.005","article-title":"The Need for Improved Vaccines against Foot-and-Mouth Disease","volume":"29","author":"Rodriguez","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.prevetmed.2013.07.013","article-title":"The Economic Impacts of Foot and Mouth Disease-What are They, How Big are They and Where do They Occur?","volume":"112","author":"Rushton","year":"2013","journal-title":"Prev. Vet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"571509","DOI":"10.3389\/fimmu.2021.571509","article-title":"Virus-Host Interactions in Foot-and-Mouth Disease Virus Infection","volume":"12","author":"Li","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/tbed.12521","article-title":"Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3-Vaccines","volume":"1","author":"Robinson","year":"2016","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.antiviral.2016.08.020","article-title":"Protection of a Novel Epitope-RNA VLP Double-Effective VLP Vaccine for Foot-and-Mouth Disease","volume":"134","author":"Dong","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198339","DOI":"10.1016\/j.virusres.2021.198339","article-title":"FMD Empty Capsids Combined with the Immunostant Particle Adjuvant -ISPA or ISA206 Induce Protective Immunity against Foot and Mouth Disease Virus","volume":"297","author":"Bidart","year":"2021","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Primavera, V., Simmons, J., Clark, B.A., Neilan, J.G., and Puckette, M. (2022). Effect of Foot-and-Mouth Disease Virus 2B Viroporin on Expression and Extraction of Mammalian Cell Culture Produced Foot-and-Mouth Disease Virus-like Particles. Vaccines, 10.","DOI":"10.3390\/vaccines10091506"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shi, X., Yang, K., Song, H., Teng, Z., Zhang, Y., Ding, W., Wang, A., Tan, S., Dong, H., and Sun, S. (2022). Development and Efficacy Evaluation of a Novel Nano-Emulsion Adjuvant for a Foot-and-Mouth Disease Virus-like Particles Vaccine Based on Squalane. Nanomaterials, 12.","DOI":"10.3390\/nano12223934"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1177\/0300985810372509","article-title":"The Early Pathogenesis of Foot-and-Mouth Disease in Cattle after Aerosol Inoculation. Identification of the Nasopharynx as the Primary Site of Infection","volume":"47","author":"Arzt","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.rvsc.2014.01.009","article-title":"Infection Dynamics of Foot-and-Mouth Disease Virus in Pigs using Two Novel Simulated-Natural Inoculation Methods","volume":"96","author":"Stenfeldt","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"685865","DOI":"10.3389\/fimmu.2021.685865","article-title":"Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles","volume":"12","author":"Salinas","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s12016-019-08769-2","article-title":"Mast Cell Biology at Molecular Level: A Comprehensive Review","volume":"58","author":"Bielory","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Katsoulis-Dimitriou, K., Kotrba, J., Voss, M., Dudeck, J., and Dudeck, A. (2020). Mast Cell Functions Linking Innate Sensing to Adaptive Immunity. Cells, 9.","DOI":"10.20944\/preprints202011.0016.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.coph.2018.05.004","article-title":"Mast cell activators as novel immune regulators","volume":"41","author":"Choi","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_15","first-page":"3917","article-title":"Cytokine Responses of Bone Marrow-derived Mast Cells to FMDV-VLPs via Mannose Receptors","volume":"53","author":"Han","year":"2022","journal-title":"Acta Vet. Zootech. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110428","DOI":"10.1016\/j.intimp.2023.110428","article-title":"Histone Acetylation Regulates BMMCs Recognition of Foot-and-Mouth Disease Virus-like Particles","volume":"121","author":"Zhang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41586-019-1411-0","article-title":"Advances in Epigenetics Link Genetics to the Environment and Disease","volume":"571","author":"Cavalli","year":"2019","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Luo, L., Gribskov, M., and Wang, S. (2022). Bibliometric Review of ATAC-Seq and Its Application in Gene Expression. Brief. Bioinform., 23.","DOI":"10.1093\/bib\/bbac061"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.genom.7.080505.115623","article-title":"Transcriptional Regulatory Elements in the Human Genome","volume":"7","author":"Maston","year":"2006","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/s41596-022-00692-9","article-title":"Chromatin Accessibility Profiling by ATAC-seq","volume":"17","author":"Grandi","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nmeth.2688","article-title":"Transposition of Native Chromatin for Fast and Sensitive Epigenomic Profiling of Open Chromatin, DNA-binding Proteins and Nucleosome Position","volume":"10","author":"Buenrostro","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.immuni.2016.10.028","article-title":"Dynamic Changes in Chromatin Accessibility Occur in CD8+ T Cells Responding to Viral Infection","volume":"45","author":"Trifari","year":"2016","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1093\/nar\/gkw1179","article-title":"Combining ATAC-seq with Nuclei Sorting for Discovery of Cis-regulatory Regions in Plant Genomes","volume":"45","author":"Lu","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_24","first-page":"906","article-title":"Lymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia","volume":"34","author":"Jing","year":"2018","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"621537","DOI":"10.3389\/fimmu.2020.621537","article-title":"Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes","volume":"11","author":"Defaus","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.5187\/jast.2021.e103","article-title":"Age-dependent Immune Response in Pigs against Foot-and-mouth Disease Virus in Vitro","volume":"63","author":"Roh","year":"2021","journal-title":"J. Anim. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"D\u00edaz-San Segundo, F., Rodr\u00edguez-Calvo, T., de Avila, A., and Sevilla, N. (2009). Immunosuppression during Acute Infection with Foot-and-mouth Disease Virus in Swine is Mediated by IL-10. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005659"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14017","DOI":"10.1038\/ncomms14017","article-title":"A Mast cell-ILC2-Th9 Pathway Promotes Lung Inflammation in Cystic Fibrosis","volume":"8","author":"Moretti","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"964","DOI":"10.4103\/0366-6999.204110","article-title":"Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis","volume":"130","author":"Yin","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.cell.2018.01.029","article-title":"The Human Transcription Factors","volume":"172","author":"Lambert","year":"2018","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1074\/jbc.M117.802900","article-title":"IL-10 Promoter Transactivation by the Viral K-RTA Protein Involves the Host-cell Transcription Factors, Specificity Proteins 1 and 3","volume":"293","author":"Miyazawa","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.4049\/jimmunol.2000985","article-title":"The Clusters of Transcription Factors NFATC2, STAT5, GATA2, AP1, RUNX1 and EGR2 Binding Sites at the Induced Il13 Enhancers Mediate Il13 Gene Transcription in Response to Antigenic Stimulation","volume":"205","author":"Kamran","year":"2020","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41597-019-0071-0","article-title":"An ATAC-seq Atlas of Chromatin Accessibility in Mouse Tissues","volume":"6","author":"Liu","year":"2019","journal-title":"Sci. Data"},{"key":"ref_34","unstructured":"(2018). Laboratory Animal\u2014Guideline for Ethical Review of Animal Welfare (Standard No. GB\/T35892-2018)."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Abbring, S., Blokhuis, B.R.J., Miltenburg, J.L., Olmedo, K.G.J.R., Garssen, J., Redegeld, F.A., and van Esch, B.C.A.M. (2020). Direct Inhibition of the Allergic Effector Response by Raw Cow\u2019s Milk-An Extensive In Vitro Assessment. Cells, 9.","DOI":"10.3390\/cells9051258"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17044\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:36:23Z","timestamp":1760132183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,1]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242317044"],"URL":"https:\/\/doi.org\/10.3390\/ijms242317044","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,1]]}}}