4 ____________________________________________________________________________ ATP-Dependent Chromatin Remodeling Corey L. Smith and Craig L. Peterson Program in Molecular Medicine University of Massachusetts Medical School Worcester, Massachusetts 01605 I. Chromatin Structure: A Short Primer II. ATP-Dependent Chromatin Remodeling Enzymes III. ATP-Dependent Chromatin Remodeling Enzymes are Involved in the Control of Numerous Cellular Processes A. The SWI2/SNF2 Complexes: Transcriptional Regulators B. ISWI Complexes: Sliding into Transcription Regulation and Chromatin Assembly C. Mi-2 Complexes: General Repressors D. Other Subfamilies: Repair and Establishing Chromatin Domains IV. Understanding the Molecular Mechanism of ATP-Dependent Chromatin Remodeling A. The SWI2/SNF2-Like ATPase Subunit is the Master Switch B. Chromatin Remodeling Enzymes are Able to Introduce Helical Torsion into DNA and Nucleosomal Substrates C. The Chromatin Remodeling Enzyme–Nucleosome Interface D. How is ATP Hydrolysis Coupled to the Generation of Remodeled Chromatin? E. Nucleosome Accessibility and Mobilization by Chromatin Remodeling Enzymes F. Disruption of Nucleosome Structure: Moving Dimers Around G. Determining How Remodeling Works In Vivo H. Remodeling at the Fiber Level V. Concluding Remarks Acknowledgments References The study of chromatin and how this dynamic structure modulates events in the eukaryotic nucleus has become an increasingly important topic in biomedical research. A large number of enzymes have been discovered that are responsible for modifying and altering chromatin structure, either globally or specifically at particular gene promoters or regions of the chromosome. This chapter provides an introduction to the structure of chromatin and then describes how special classes of enzymes modulate chromatin structure to allow access to DNA. C 2005, Elsevier Inc. I. Chromatin Structure: A Short Primer The structure and function of chromatin is inherently dynamic. During mitosis, individual chromatids become highly compact, align on the metaphase plate, Current Topics in Developmental Biology, Vol. 65 Copyright 2005, Elsevier Inc. All rights reserved. 0070-2153/05 $35.00 115