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First published online 14 September 2004
doi: 10.1242/jcs.01229

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Quantitative signature for architectural organization of regulatory factors using intranuclear informatics

¹ Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655-0106, USA
² Program in Molecular Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655-0106, USA

^* Author for correspondence (e-mail: gary.stein{at}umassmed.edu)

Accepted 18 March 2004

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.

Key words: Nuclear architecture, Runx (AML/Cbfa), Informatics, Quantitative, Transcription

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