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Critical Reviews™ in Eukaryotic Gene Expression
IF: 1.841 5-Year IF: 1.927 SJR: 0.649 SNIP: 0.516 CiteScore™: 1.96

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v20.i2.50
pages 149-155

Architectural Genetic and Epigenetic Control of Regulatory Networks: Compartmentalizing Machinery for Transcription and chromatin remodeling in nuclear Microenvironments

Gary S. Stein
Department of Biochemistry University of Vermont 149 Beaumont Ave., HSRF 326 Burlington, VT 05405
Andre J. van Wijnen
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655
Anthony N. Imbalzano
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School and Cancer Center, Worcester, Massachusetts
Martin Montecino
Centro de Investigaciones Biomedicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, Santiago
Sayyed Kaleem Zaidi
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655
Jane B. Lian
Department of Biochemistry University of Vermont 89 Beaumont Ave., Given E210B Burlington, VT 05405
Jeffrey A. Nickerson
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School and Cancer Center, Worcester, Massachusetts
Janet L. Stein
Department of Biochemistry, University of Vermont 89 Beaumont Ave., Given E210E Burlington, VT 05405

ABSTRACT

The regulatory machinery that governs genetic and epigenetic control of gene expression for biological processes and cancer is organized in nuclear microenvironments. Strategic placement of transcription factors at target gene promoters in punctate microenvironments of interphase nuclei supports scaffolding of co- regulatory proteins and the convergence as well as integration of regulatory networks. The organization and localization of regulatory complexes within the nucleus can provide signatures that are linked to regulatory activity. Retention of transcription factors at gene loci in mitotic chromosomes contributes to epigenetic control of cell fate and lineage commitment, as well as to persistence of transformed and tumor phenotypes. Mechanistic understanding of the architectural assembly of regulatory machinery can serve as a basis for treating cancer with high specificity and minimal off-target effects.


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