Chromatin remodeling

Chromosome involves the fine design of DNA and protein complex. It also involves few non-histone proteins performing various functions. The compact structure of chromosomes fits them in the nucleus of the cell. The eukaryotic chromatin organization includes an inbuilt system of regulation. Hence, it does not require an additional repressor molecule to control the gene expression. It is the main feature of eukaryotic regulation of gene expression. The prokaryotic gene expression consists of operons such as Lac and the tryptophan operons. They require repressors to bind with the respective operators and prevent the transcription of the structural genes. However, the eukaryotic systems have their own mechanisms independent of the repressors. Hence, they save their machinery and material from making the repressor molecules. 

Repression of gene activity:

Image: Chromatin remodeling

The eukaryotic nucleosome organization shows a repressive effect on the gene expression. Hence, it does not include the extra repressors. The eukaryotic genes involve two main types based on the transcription such as the transcriptionally active genes and the transcriptionally inactive genes. The enzymes known as nucleases degrade or interact with the DNA molecules. The transcriptionally active genes show sensitivity to the DNase-I. The transcriptionally inactive genes do not sensitivity to the DNase-I. The transcriptionally active and inactive genes get distinguished by a restriction digest and a southern blot. Process the cells for obtaining the chromatin. Treat the chromatin with the DNase-I enzyme. The process of restriction digestion involves treatment of the DNA with the restriction enzyme. The enzyme cleaves the DNA to form fragments of different sizes. Hence, it targets the restriction sites.

The fragments get separated by gel electrophoresis followed by Southern blotting and autoradiography. The studies reveal two types of genes. One type of genes shows accessibility to the DNase-I. The other type of genes does not allow the DNase-I access. The genes accessible to the DNase-I consists of few fragments or no fragments. These regions involve a less coiled DNA. The less coiled DNA expose more hypersensitive sites near the transcriptionally active sites. These regions show very high sensitivity. They are present upstream of the transcription start site. The non-accessible regions involve more and more coiling. Hence, they show the whole gene. Due to very high coiling, they do not expose the genes to DNase-I.

The histone proteins also repress the gene expression. Suppose DNA gets simultaneously treated with histones and promoter binding protein. In this case, the histones compete more strongly for the promoters. They form nucleosomes at TATA box of the core promoter. The promoter binding proteins do not get a chance to bind with the promoters. Hence, the transcription does not occur. Suppose if the DNA first binds with the promoter binding protein. The proteins get assembled to the TATA box, thereby blocking the nucleosome assembly. Hence, it results in the transcription of the genes. The third possibility involves the treatment of DNA with the promoter binding proteins and activators. The activators bind with the enhancers thereby allowing the promoter binding proteins to bind to the TATA box. Hence, transcription occurs.

Activation of genes by chromatin remodeling:

Gene activation involves a key event related to the chromatin structure. It alters the chromatin structure in the vicinity of the core promoter. It is known as the chromatin remodeling. Two types of chromatin remodelers include nucleosome modifying enzymes and the ATP-dependent nucleosome remodeling complex. The nucleosome modifying enzymes conduct acetylation or deacetylation of the core histones.

Let us consider the nucleosome modifying enzymes. The histone acetyltransferases help in the acetylation process. The histone acetyltransferases get recruited to the chromatin. The activators interact with the DNA binding sites in the presence of the histone acetyltransferases and acetylate the lysine residues. Mainly the amino-terminal tails of the core histones have the lysine residues. Thus, the histones slowly lose the affinity for the DNA. Due to the acetylation, the chromatin structure gets reduced from the 30 nm to the 10 nm. Now the promoters become more accessible for the transcription. The TFIID binds to the site and allows transcription. The acetylated structures get deacetylated by another class of enzymes known as histone deacetylases. These enzymes remove the acetyl groups and restore the 30nm fiber.

ATP-dependent nucleosome remodeling complexes involve a large multiprotein complex. They help in remodeling the chromatin. They use ATP hydrolysis for obtaining energy. The activators interacting with the DNA binding sites recruit nucleosome remodeling complexes. These complexes alter the nucleosome. Thus, the transcription machinery binds to the promoter. An example includes SW1/SNF ATP-dependent nucleosome remodeling complex in yeast.

References:

[1] Epigenetics, Lyle Armstrong
[2] Human Molecular Genetics, Tom Strachan, Andrew Read

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