A Dynamic System of Accetylating and Deaccetylating Factors Has Effects on Transcription

Specific sequences in DNA recruit transcription factors, called activators and repessors, coactivators and corepressors. In order for DNA to be transcribed and expressed, the chromatin needs to be decondensed (accetylated) to allow for there to be enough space for these transcription factors to bind. For a transcription factor to bind, it binds to a histone acetyl-transferase, which unfolds the chromatin.

However, either side of the recruitment position has deacetylating enzymes. This creates a battle of kinetics and equilibrium shifts, where the two forces of accetylation and deacetylation are competing to determine the outcome of whether or not the transcription factor can bind to the region. Also, the success of transcription depends on how long the transcription factor can bind. If the factor is easily displaced, transcription cannot occur.

It is possible for heterochromatin to have an activator bind to a promoter, but it is less probable because of reaction kinetics. In the lab, if decondensation is required for a highly deaccetylated region, viral components are used to induce this process.

There are other chromatin modifications, which contribute to a histone code. The histones are modified in different ways to alter the charge and the overall surface of the protein, which effects the binding properties. Common alterations include phosphorylation, mono-ubiquitination, and methylation.

Phosphorylation, mono-ubiquitination, and methylation lead to either activation or repression of the gene depending on location of the modification. If we examine more closely the effects of methylation in particular, the properties of the three methyl groups bound to the histone cause the amine function to be blocked, and the positive charge to be maintained. This, in turn, blocks acetylation, which means the chromatin in that region will be condensed, and it is unlikely transcription will occurs.

Each of the histone modification reactions is reversible and carried out by enzymes.

In addition to the above methods to modify chromatin structure, chromatin remodeling mediated by chromatin remodeling complexes also is possible. The complexes detach the strong interactions of the histones with the DNA, in a way that does not completely remove them, but makes the DNA more accessible.

The process of initiating transcription is dynamically controlled by access to the DNA regions and how tightly the chromatin is bound.

Note:

Recall that acetylation is when the lysine residues in histones are bound to an acetyl group, making the positive amino acid neutral. This prevents the interaction of the histones with the negative phosphate backbone of the DNA, and the chromatin is decondensed, allowing easier access for transcription factors to bind, and gene expression to take place. On the other hand, deaccetylated histones do not have the acetyl group bound, and the lysine residues maintain their positive charge and are attracted to the phosphate backbone of the DNA, causing the chromatin to be condensed, and reducing expression.