Gene Chromatin

Wu C (1984b) Activating protein factor binds in vitro to upstream control sequences in heat shock gene chromatin. Nature 311 81-84... 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

A model called histone code theory includes more aspects of chromatin regulation which have been identified. The histone code theory predicts that histone acetylation and other posttranslational histone modifications serve as binding sites for regulatory proteins which mediate processes like gene transcription upon recruitment (see Fig. 2b) [3]. In this context histone modifications can be understood as... 

Turner BM (2001) Chromatin and Gene Regulation. Blackwell Science Ltd., Oxford... 

Histone tails are the N-terminal regions of histones which reach outside the nucleosomes. They are not essential for the formation in of nucleosomes but are required for the formation of higher-order chromatin structures. The histone tails are also known to be heavily posttranslationally modified by acetylation, phosphorylation, methylation, etc. and are important for the regulation of gene activity. 

Proteins that bind DNA at specific DNA sequences often distal from transcriptional start sites of genes. Their binding and activity is usually cell type or stimulus triggered, which subsequently decondensate the chromatin and finally lead to the recruitment of general transcription factors and the RNA polymerase. 

All steps—from changes in DNA template, sequence, and accessibility in chromatin to RNA stability—are subject to modulation and hence are potential control sites for eukaryotic gene regulation. 

Chromatin Remodeling Is an Important Aspect of Eukaryotic Gene Expression... 

Some of this differential expression is achieved by having different regions of chromatin available for transcription in cells from various tissues. For example, the DNA containing the P-globin gene cluster is in active chromatin in the reticulocyte but in inactive chromatin in muscle cells. All the factors involved in the determination of active chromatin have not been elucidated. The presence of nucleosomes and of complexes of histones and DNA (see Chapter 36) certainly provides a barrier against the ready association of transcription fac-... 

Finally, the binding of specific transcription factors to cognate DNA elements may result in disruption of nucleosomal structure. Many eukaryotic genes have multiple protein-binding DNA elements. The serial binding of transcription factors to these elements—in a combinatorial fashion—may either directly disrupt the structure of the nucleosome or prevent its re-formation or recruit, via protein-protein interactions, multiprotein coactivator complexes that have the ability to covalently modify or remodel nucleosomes. These reactions result in chromatin-level structural changes that in the end increase DNA accessibifity to other factors and the transcription machinery. 

The cis-acting elements that decrease or repress the expression of specific genes have also been identified. Because fewet of these elements have been smdied, it is not possible to fotmulate genetalizations about their mechanism of action—though again, as for gene activation, chromatin level covalent modifications of histones and other proteins by (repressor)-recruited multisubunit corepressors have been imphcated. 

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