UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology; Program in Molecular Medicine
Date
9-16-2004
Document Type
Article
Medical Subject Headings
Animals; Biochemistry; Cell Line, Tumor; Cell Nucleus; Chromatin; Computational Biology; Core Binding Factor alpha Subunits; DNA-Binding Proteins; *Gene Expression Regulation; Hela Cells; Humans; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Mitosis; Mutation; Neoplasm Proteins; Nuclear Matrix; Nuclear Proteins; Point Mutation; Protein Structure, Tertiary; Rats; Transcription Factors; Transcription, Genetic
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Regulatory machinery for replication and gene expression is punctately organized in supramolecular complexes that are compartmentalized in nuclear microenvironments. Quantitative approaches are required to understand the assembly of regulatory machinery within the context of nuclear architecture and to provide a mechanistic link with biological control. We have developed 'intranuclear informatics' to quantify functionally relevant parameters of spatially organized nuclear domains. Using this informatics strategy we have characterized post-mitotic reestablishment of focal subnuclear organization of Runx (AML/Cbfa) transcription factors in progeny cells. By analyzing point mutations that abrogate fidelity of Runx intranuclear targeting, we establish molecular determinants for the spatial order of Runx domains. Our novel approach provides evidence that architectural organization of Runx factors may be fundamental to their tissue-specific regulatory function.
Rights and Permissions
Citation: J Cell Sci. 2004 Oct 1;117(Pt 21):4889-96. Epub 2004 Sep 14. Link to article on publisher's site