Nuclear organization mediates cancer-compromised genetic and epigenetic control
Department of Pediatrics; Department of Biochemistry and Molecular Pharmacology; UMass Metabolic Network; Nickerson Lab; Imbalzano Lab
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
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.
DOI of Published Version
Adv Biol Regul. 2018 May 9. pii: S2212-4926(18)30078-2. doi: 10.1016/j.jbior.2018.05.001. [Epub ahead of print] Link to article on publisher's site
Advances in biological regulation
Zaidi SK, Fritz AJ, Tracy KM, Gordon JA, Tye CE, Boyd J, Van Wijnen AJ, Nickerson JA, Imbalzano AN, Lian JB, Stein JL, Stein GS. (2018). Nuclear organization mediates cancer-compromised genetic and epigenetic control. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.jbior.2018.05.001. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1592