Zaidi Sayyed K, Fritz Andrew J, Tracy Kirsten M, Gordon Jonathan A, Tye Coralee E, Boyd Joseph, Van Wijnen Andre J, Nickerson Jeffrey A, Imbalzano Antony N, Lian Jane B, Stein Janet L, Stein Gary S
Department of Biochemistry and University of Vermont Cancer Center, University of Vermont, Burlington, VT, United States.
Departments of Orthopedic Surgery, Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, United States.
Adv Biol Regul. 2018 Aug;69:1-10. doi: 10.1016/j.jbior.2018.05.001. Epub 2018 May 9.
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2. Contributions of chromatin remodeling to breast cancer nuclear morphology, metabolism and effectiveness of chemotherapy; 3. Relationships between fidelity of nuclear organization and metastasis of breast cancer to bone; 4. Dynamic modifications of higher-order inter- and intra-chromosomal interactions in breast cancer cells; 5. Coordinate control of cell growth and phenotype by tissue-specific transcription factors; 6. Oncofetal epigenetic control by bivalent histone modifications that are functionally related to sustaining the stem cell phenotype; and 7. Noncoding RNA-mediated regulation in the onset and progression of breast cancer. The discovery of components to nuclear organization that are functionally related to cancer and compromise gene expression have the potential for translation to innovative cancer diagnosis and targeted therapy.
核组织在功能上与基因表达的遗传和表观遗传调控相联系，以实现生物控制，并且在癌症中会发生改变。核组织通过促进染色体、基因和调控复合物在动态三维微环境中的生理反应性相互作用，来支持正常细胞和癌细胞的生长及表型特性。我们将综述核结构/功能关系，其中包括：1. 表型转录因子对基因进行表观遗传标记，以控制细胞进入和退出有丝分裂时基因表达的保真度和可塑性；2. 染色质重塑对乳腺癌核形态、代谢及化疗效果的影响；3. 核组织保真度与乳腺癌向骨转移之间的关系；4. 乳腺癌细胞中染色体间和染色体内高阶相互作用的动态修饰；5. 组织特异性转录因子对细胞生长和表型的协同控制；6. 与维持干细胞表型功能相关的二价组蛋白修饰对肿瘤胎儿的表观遗传控制；7. 非编码RNA介导的调控在乳腺癌发生和发展中的作用。发现与癌症功能相关且影响基因表达的核组织成分，有可能转化为创新的癌症诊断和靶向治疗方法。
