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Critical Reviews™ in Eukaryotic Gene Expression

Impact factor: 1.660

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v6.i2-3.40
pages 149-188

The Nucleosomal Array: Structure/Function Relationships

Terace M. Fletcher
The Cancer Therapy and Research Center, Institute for Drug Development, 14960 Omicron Dr., San Antonio, TX 78245-3217
Jeffrey C. Hansen
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7760

ABSTRACT

A nucleosomal array consists of core histone octamer-DNA complexes spaced at ∼200 bp intervals along a DNA molecule. Nucleosomal arrays are the fundamental building block of chromosomal superstructures, the substrate for transcription, and the first nucleoprotein assembly laid down after DNA replication. The development of homogeneous length-defined nucleosomal arrays has led to a greatly improved understanding of nucleosomal array structural dynamics in the solution state. Under physiological salt conditions, a nucleosomal array is in dynamic equilibrium between folded, self-associated and dissociated conformational states. Folding and self-association are both critically dependent on the core histone tail domains, consistent with an essential functional role for the tail domains in the mediation of chromosomal level DNA compaction in the nucleus. Nucleosomal array folding is repressive to transcription in vitro, but can be overcome by compositional (e.g., tail domain acetylation) and configurational (e.g., histone octamer depletion) changes that are correlated with transcriptional activation in vivo. The mechanism of replication-coupled chromatin assembly also appears to be functionally linked to the dynamic properties of nucleosomal arrays. Although once thought to be both structurally and functionally inert, it is now apparent that the nucleosomal array is a key participant in the biological processes that take place within the chromosomal fibers of eukaryotes.