Quarterly Reviews of Biophysics



Review Article

Role of DNA sequence in nucleosome stability and dynamics


J.  Widom  a1 c1
a1 Department of Biochemistry, Molecular Biology, and Cell Biology, and Department of Chemistry, Northwestern University, 2153 Sheridan Road, Evanston, Illinois 60208-3500, USA

Abstract

1. Introduction 270

1.1 Overview of nucleosome structure 271

2. Relative equilibrium stability (affinity) of histone–DNA interactions in nucleosomes 272

2.1 Relative affinity equals relative equilibrium stability 272

2.2 Competition assays for relative free-energy measurements 273

2.3 Technical issues in relative free-energy measurements 275

2.4 Range of affinities 278

3. Relation of nucleosome stability to nucleosome positioning 279

3.1 Translational nucleosome positioning 279

3.2 Rotational positioning 280

3.3 Unfavorable positioning 281

3.4 Experiments 281

4. Physical basis of DNA sequence preferences 282

4.1 Free-energy cost of DNA bending 283

4.2 Molecular mechanics of DNA bending and bendability 284

4.3 Bent and bendable DNA sequences 286

4.4 Parameter sets for prediction of DNA bending and bendability 288

4.5 DNA twisting 290

4.6 Energetics of nucleosomal DNA packaging 291

5. DNA sequence motifs for nucleosome packaging 292

5.1 Natural and designed nucleosomal DNAs 293

5.2 New rules and reagents from physical selection studies 294

5.3 Molecular basis of DNA sequence preferences 299

5.4 Special properties of the TA step 300

5.5 Unfavorable sequences 302

5.6 Natural genomes 303

5.7 Evolutionary approach toward an optimal sequence 305

5.8 Optimization by design 305

6. Dynamic nucleosome instability 308

6.1 Site-exposure equilibria 308

6.2 DNA sequence-dependence to site-exposure equilibria 312

6.3 Nucleosome translocation 315

6.4 Action of processive enzymes 319

7. Conclusions 319

8. Acknowledgements 320

9. References 320

The nucleosome core particle is the fundamental repeating subunit of chromatin. It consists of two molecules each of the four ‘core histone’ proteins, H2A, H2B, H3 and H4, and a 147 bp stretch of DNA. The lowest level of chromatin organization consists of a repeated array of nucleosome core particles separated by variable lengths of ‘linker DNA’. In many, but not all, cases, each core particle plus its linker DNA is associated with one molecule of a fifth ‘linker’ histone protein, H1. The complex of the core particle plus its linker DNA and H1 (when present) is called a ‘nucleosome’.


Correspondence:
c1 Correspondence: J. Widom, Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, IL 60208-3500, USA. Tel.: 847/467-1887; Fax: 847/467-1380; E-mail: j-widom@northwestern.edu