{"title":"Chromatin structure and gene transcription of recombinant p53 adenovirus vector within host.","authors":"Duo Ning, Yuqing Deng, Simon Zhongyuan Tian","doi":"10.3389/fmolb.2025.1562357","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The recombinant human p53 adenovirus (Ad-p53) offers a promising approach for cancer therapy, yet its chromatin structure and effects on host chromatin organization and gene expression are not fully understood.</p><p><strong>Methods: </strong>In this study, we employed <i>in situ</i> ChIA-PET to investigate the colorectal cancer cell line HCT116 with p53 knockout, comparing them to cells infected with the adenovirus-vector expressing p53. We examined alterations in chromatin interactions and gene expression following treatment with the anti-cancer drug 5-fluorouracil (5-FU).</p><p><strong>Results: </strong>Our results indicate that Ad-p53 forms a specific chromatin architecture within the vector and mainly interacts with repressive or inactive regions of host chromatin, without significantly affecting the expression of associated genes. Additionally, Ad-p53 does not affect topologically associating domains (TADs) or A/B compartments in the host genome.</p><p><strong>Discussion: </strong>These findings suggest that while Ad-p53 boosts p53 expression, enhancing drug sensitivity without substantially altering host HCT116 chromatin architecture.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1562357"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906465/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2025.1562357","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The recombinant human p53 adenovirus (Ad-p53) offers a promising approach for cancer therapy, yet its chromatin structure and effects on host chromatin organization and gene expression are not fully understood.
Methods: In this study, we employed in situ ChIA-PET to investigate the colorectal cancer cell line HCT116 with p53 knockout, comparing them to cells infected with the adenovirus-vector expressing p53. We examined alterations in chromatin interactions and gene expression following treatment with the anti-cancer drug 5-fluorouracil (5-FU).
Results: Our results indicate that Ad-p53 forms a specific chromatin architecture within the vector and mainly interacts with repressive or inactive regions of host chromatin, without significantly affecting the expression of associated genes. Additionally, Ad-p53 does not affect topologically associating domains (TADs) or A/B compartments in the host genome.
Discussion: These findings suggest that while Ad-p53 boosts p53 expression, enhancing drug sensitivity without substantially altering host HCT116 chromatin architecture.
期刊介绍:
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.