Roberto Viau

Notes on:


Nucleosomes are involved in some way in the regulation of transcription. It was thought they were mostly involved in repressing it. The nucleosome consists of a tetramer of H3 and H4 plus two dimmers. Mutations on the histones affect with specificity the expression of some gene. This selectivity seems to depend on the assembly of specific nucleoproteic architectures.


The amino terminals of the histone molecules are involved in blocking the TFIIA. Experimental evidence shows that either acetylating or removing these regions increase the transcription rate. The nucleosome, however, is not displaced in these reactions. It is believed that the long or absent tail allow protein factors to interact with the DNA. Whenever the tail is deacetylated, the transcription stops. This implies there must be some equilibrium between deacetylase and acetylase. This allows chromatin to be remodeled.


Rpd3p is believed to amplify regulatory effects. It does not bind to DNA, but instead seems to interact with transcription regulators. These regulators, like Sin3p, interact with other proteins, having protein-protein interactions. Usually its effect is repressive. Rpd3p may enhance Sin3p favoring deacetylation. Deacetylation facilitates the association of other repressors within the chromosome. Rpd3p may also be required for packaging DNA into restricted chromatin environments. Without deacetylation, a large number of nonproductive interactions are likely to occur. This is, chromatin packaging limits the available interaction places, so Rpd3p may promote packaging in a way only some sites are available for further regulation.


As it can be expected there are proteins that interact directly with the nucleosome. For example, the SW12/SNF2. This family contains an ATPase domain, and are believed to cause structural changes in chromatin structure. This remodeling is thought to increase the accessibility of DNA to other regulatory proteins. Original evidence suggested SW12/SNF2 interacted with the DNA itself, but now it is know it assists some other protein to reach it. It is now known that SW12/SNF2 induce an ATP dependent change in the nucleosome, without disrupting it. The change promotes binding of general transcription factors (TataBindingProtein, GAL4). However, it was not explained why the TBP could only bind to a specific TATA. Probably SW12/SNF2 associates with DNA binding proteins that recognize the modification target. This remodeling may allow one of these factors to interact with the DNA or allow other factors to interact with the originally hidden site.


More evidence on nucleosomes related with transcription arise from the fact that when they are present some factors seem to work better. Probably the nucleosome physically brings a regulating and a transcribing region together.


In conclusion, the nucleosome plays an important role regulating gene expression. It can either expose or hide a regulating site to its effectors. This can be achieved by acetylating/ deacetylating, ATP dependent changing, or physically bringing together the sites of interest.


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