ABSTRACT
Contents 4.1 Elements of chromatin structure .......................................................... 68
4.1.1 Determinants of nucleosome positioning ................................ 69 4.1.2 Nucleosomes and elongation ..................................................... 71 4.1.3 Chromatin folding ....................................................................... 71 4.1.4 Histone flavors and chromatin accessories ............................. 71 4.1.5 Chromatin replication and histone chaperones ...................... 72 4.1.6 Heterochromatin versus euchromatin ..................................... 73 4.1.7 HP1-mediated heterochromatin ................................................ 74 4.1.8 Polycomb and trithorax group genes maintain silenced and active chromatin domains .................................. 75 4.1.9 X inactivation ............................................................................... 77
4.2 Covalent histone tail modifications ...................................................... 78 4.2.1 Histone acetylation ...................................................................... 80
4.2.1.1 HATs .............................................................................. 80 4.2.1.2 HDACs ........................................................................... 82 4.2.1.3 Acetylation is a short-duration epigenetic mark ..... 82 4.2.1.4 Specific acetylation of H4K16 prevents
chromatin folding ........................................................ 83 4.2.1.5 Acetylated lysines are protein-protein
interaction surfaces ...................................................... 83 4.2.2 Histone methylation .................................................................... 84
4.2.2.1 Lysine and arginine methyltransferases .................. 84 4.2.2.2 Lysine and arginine demethylases ............................ 85 4.2.2.3 Histone methylation controls protein
recruitment to chromatin ............................................ 86 4.2.2.4 Interplay between acetylation
and methylation ........................................................... 87 4.2.3 Histone phosphorylation, ubiquitination, and other modifications .............................................................. 87
4.3 ATP-dependent chromatin remodeling complexes ............................ 88 4.3.1 Nucleosome movement and spacing ........................................ 90 4.3.2 Formation of structurally altered nucleosomes ...................... 91 4.3.3 General roles in nucleosome deposition .................................. 92 4.3.4 Targeted histone removal and redeposition ............................ 92 4.3.5 Histone replacement ................................................................... 93 4.3.6 Cooperation between chromatin remodeling complexes and other chromatin effects ....................................................... 93 4.3.7 Remodeling complexes in epigenetic regulation? .................. 94
4.4 Conclusions .............................................................................................. 94 4.4.1 Maintenance of chromatin modifications ................................ 95 4.4.2 Cooperation between CpG methylation and chromatin changes .............................................................. 95
References .......................................................................................................... 96
The chromatin packaging of eukaryotic DNA is neither uniform nor random. In the last few decades it has become increasingly clear that the precise regulation of chromatin structures is essential for the proper control of DNA accessibility, controlling transcription, replication, recombination and repair. This chapter will provide an introduction to basic elements of chromatin structure, and then introduce the range of covalent modifications and noncovalent structural alterations that play into regulation of DNA accessibility in chromatin. As we will see, chromatin modifications have great potential as epigenetic control mechanisms, in that they can control DNA accessibility in a way that is not directly dependent on underlying DNA sequence and (at least for certain modifications) that they can persist for long periods of time. Chromatin modifications do not appear to be epigenetic marks that can be inherited from one generation of organisms to the next. Rather, they are “somatic cell epigenetic marks” that are used to control patterns of DNA accessibility through somatic cell divisions or over long periods of time in nondividing differentiated cells. That is not to say that chromatin modifications are not important for heritable epigenetic effects, such as genomic imprinting. Indeed, the functional effects of CpG methylation marks are largely caused by the differential recruitment of chromatin modifying enzymes.
