Scaffold Matrix Attachment Regions SMARs Relevance for Disease and Therapy


1 Introduction 68

1.1 Relevance of Non-Coding DNA: "Junk-DNA" and Gene Deserts 69

2 Scaffold/Matrix Attachment Regions (S/MARs): DNA at the Scaffold 73

2.1 S/MAR Aberrations and Disease 75

2.2 BURs as Targets for Anticancer Therapy 76

3 Scaffolding: Ubiquitous Fibre-Forming Components and Their Associated Functions 78

3.1 Lamin Networks 78

3.2 hnRNPs: SAF-A 80

3.3 Nuclear Actin 82

3.4 Nuclear Mitotic Apparatus Protein (NuMA) 82

4 Regulatory Networks: Key Players Qualify by Diverse

Interactions with S/MARs or Scaffolds 83

4.2 S/MAR-Dependent Interactions at the IgH Enhancer 92

5 Outlook and Perspectives 95

References 98

Abstract There is increasing awareness that processes, such as development, aging and cancer, are governed, to a considerable extent, by epigenetic processes, such as DNA and histone modifications. The sites of these modifications in turn reflect their position and role in the nuclear architecture. Since epigenetic changes are easier to reverse than mutations, drugs that remove or add the chemical tags are at the forefront of research for the treatment of cancerous and inflammatory diseases. This review will use selected examples to develop a unified view that might assist the systematic development of novel therapeutic regimens.

J. Bode

Both authors contributed equally (A.G.: nuclear structure and function; M.V.: epigenetic properties of PARP)

[email protected]

E. Klussmann, J. Scott (eds.) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology 186, © Springer-Verlag Berlin Heidelberg 2008

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