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.