Nucleosome transcriptional regulation

Workman JL and Kingston RE (1998) Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu Rev Biochem 67 545-579... 

Studies over the last 10 years clearly demonstrate the importance of histone variants in modifying nucleosome structure and function. They play specialized roles in diverse chromatin functions including transcriptional regulation, DNA repair, chromosome segregation, spermatogenesis, and histone replacement. 

The contribution of individual core histone N-tails to transcriptional regulation has been recently addressed in a reconstitution study [42]. Varied combinations of recombinant and mutant cores histones have been assembled on circular plasmids, and the resultant nucleosomal arrays were tested for transcriptional... 

Histones are basic proteins that are made up by a globular domain and an N-terminal tail that protrudes from the nucleosome. Nucleosomes form the basic unit of chromatin and are made up by a complex of DNA wrapped around an octamer of histones formed by pairs of the histones H2A, H2B, H3, and H4 (45,46) (Fig. 1). Post-translational modification of the core histone tails by methylation, acetylation, phosphorylation, ubiquitina-tion, or sumoylation can alter the structure of the nucleosomes and thus alter gene expression. These post-translational modifications determine the structure and pattern of chromatin condensation and determine the histone code that drives gene transcriptional regulation (47,48). Below are briefly described the factors determining the histone acetylation and methylation. 

Fig. 1.37 Model of enhanceosome function during transcription activation. The requirement for only a single regulator or multiple transcriptional regulators, organized in the enhanceosome, may depend on the state of chromatin. In chromatin state 1, the promotor is covered by a nucleosome and binding of three regulators (circle, square, triangle) is required to achieve effective recruitment of chromatin modification complexes and to free the promotor for binding of the RNA polymerase ho-...

There are a number of different ways by which chromatin remodeling can occur. Removal, destabilization, or mobilization of nucleosomes may regulate access of transcription factors to genomic DNA for transcriptional activation. Posttranslational modification of histone proteins can also affect chromatin structure, which occurs most usually at the N-terminal tails of the histones and... 

In eukaryotes, transcriptional regulation is mediated within the context of nucleosomes, the repeating subunits of chromatin. The core nucleo-some particle consists of 147 base pairs of DNA wrapped around the histone octamer composed of two copies of each of the four core histones H2A, H2B, H3, and H4. Each core histone is composed of a globular domain and an unstructured amino-terminal tail of 25-40 residues. This... 

What is the relevance of these observations to transcriptional control If, indeed, the tails become more loosely associated with DNA upon hyperacetylation, it is possible that the underlying DNA becomes more accessible to nonhistone regulators. In vitro experiments with purified chromatin components and particular transcriptional regulators (A. Wolffe, J. Workman, and their colleagues) have found that histone hyperacetylation potentiates binding to nucleosomal substrates by such proteins as TFIIIA, Gal4, and USF. Whether such potentiation of binding occurs in vivo is unknown. 

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