Biomechanical properties of chromatin in cancer and normal cells

癌症和正常细胞染色质的生物力学特性

• 批准号: 10702505
• 负责人: YAMINI P DALAL
• 金额: $ 82.29万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702505
• 关键词: Address; Aging; Biology; Biomechanics; Biophysics; Cells; Centromere; Chromatin; Chromosomes; Crowding; Disease; Epigenetic Process; Genome; Genomics; Goals; Histones; Malignant Neoplasms; Mitosis; Normal Cell; Nuclear; Oncogenic; Paper; Phenotype; Polymers; Process; Property; Publishing; Seminal; Stress; Stretching; Variant; Work; cancer cell; daughter cell; epigenome; field study; mechanical properties; response

In 2019, we published a seminal paper showing that mechanical properties of chromatin are encoded in the histone variants which epigenetically and structurally mark specialized loci like centromeres. Since that work, several papers have also been published in the field studying this phenomenon on a global genomic scale. Our current work attempts to bring together biophysical questions to the cancer and aging epigenome, to understand whether changes in stretching, crowding, or other properties of chromatin are altered with disease, and if so, which factors underlie these changes. We then anticipate asking whether reversal of such factors might restore integrity to the chromatin meshwork, thereby suppressing oncogenic or aging related phenotypes in the nuclear response to strain/stress.

2019年，我们发表了一篇开创性的论文，表明染色质的机械性质编码在组蛋白变体中，组蛋白变体在表观遗传和结构上标记着丝粒等特殊基因座。自那项工作以来，在全球基因组范围内研究这一现象的领域也发表了几篇论文。我们目前的工作试图将癌症和衰老的表观基因组的生物物理学问题结合在一起，以了解染色质的拉伸、拥挤或其他属性的变化是否会随着疾病而改变，如果是这样的话，哪些因素是这些变化的基础。然后，我们预计会询问这些因素的逆转是否可以恢复染色质网络的完整性，从而抑制核对应变/应激反应中的致癌或衰老相关表型。