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Histones, Histone Modifications, and the Inheritance of Chromatin Structure

Stefan U. Kass, Alan P. Wolffe


The replication of the genome during S phase represents a crucial period for the establishment and maintenance of programs of differential gene activity. Duplication of the chromosome requires the reassembly of the precise nucleoprotein complexes directing gene transcription or repression. The maintenance of chromosomal structures through replication reflects the commitment of a defined cell type or line to a particular state of determination. This influence of preexisting protein/DNA interactions in a parental chromosome on the structure and function of daughter chromosomes therefore reflects an epigenetic imprint. In this chapter, we consider the events occurring at the eukaryotic replication fork, their consequences for preexisting chromosomal structures, and how an epigenetic imprint might be maintained.

The primary requirement for transcription is the association of the basal transcriptional machinery (including the TATA-binding protein, TBP) with the promoter. This machinery directs the recruitment of RNA polymerase (I, II, or III) dependent on the exact TBP-associated factors (TAFs). A wide variety of sequence-specific transcription factors influence the recruitment of TBP, TAFs, the general transcription factors (GTFs; e.g., TFIIB), or RNA polymerase to the promoter and their subsequent activity once they have been recruited. The recognition sites for sequence-specific transcription factors can be found many thousands of base pairs of DNA away from the promoter. They generally occur in clusters of binding sites spread over several hundred base pairs, known as enhancers and locus control regions (LCRs). The compaction of DNA mediated by various aspects of chromatin structure may...

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