Transcription activator Nucleosome

The core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

One of the most-studied covalent modifications is the acetylation of the lysine residues of histone tails. The acetylation state of lysines of nucleosomal histones modulates chromatin structure and regulates gene transcriptional activity. The balance of lysine acetylation is controlled by the antagonistic action of two enzyme families histone deacetylases (HDACs) and histone acetyltransferases (HATs). In humans there are essentially three main HDAC subclasses [6]. 

The structure of the nucleosome is affected by ionic environment. The low ion concentration makes a nucleosomal array well spread whereas 100 mM NaCl induces nucleosome-nucleosome interaction (Hizume et al, 2005 Nakai et al, 2005 Olins and Olins, 1972 Thoma et al, 1979). In vitro transcription system has been applied to understand the relationship between the nucleosome assembly and transcription activity. The results demonstrated that a positive super-coiling introduced during the progress of RNA polymerase makes the nucleosomes ahead of the polymerase unstable (Pfaffle et al, 1990). 

A system such as this can provide a powerful mechanism for transcriptional control. While bound to nucleosomes, PARP-1 promotes a transcriptionally repressed state, but one that is simultaneously poised for activation because of the allosteric activating effect of nucleosomes on PARP-1 enzymatic activity. In the presence of NAD+, PARP-1 can autoPARylate and release from nucleosomes, shifting the chromatin to a more transcriptionally active conformation. PARC can reset the system by cleaving the PAR chains from PARP-1, allowing PARP-1 to re-bind the nucleosomes and re-establish a transcriptionally repressed state. 

Stem could not form in the yeast filament, where most nucleosomes may adopt the open conformation (nucleosomes 4 and 7 in Fig. 7(b)). This in turn would be consistent with yeast chromatin high transcriptional activity [87] and DNA thermal flexibility [88,89]. 

---