Changes in Chromatin Structure during Transcription

In this article we will discuss about the changes in chromatin structure during transcription.

Displacement of nucleosomes:

During transcription, some changes in the chromatin structure occur in the region of transcription. RNA polymerase is comparatively larger in size than the nucleosomes. The molecular weight of RNA polymerase is about 5,00,000 Daltons, while that of nucleosome is about 2,60,000 Daltons.

Lewin in 1994 indicated that RNA polymerase binds to a region of about 50 bp DNA which includes 12 bp of single-stranded region involved in transcription. Now, the question arises whether the region of DNA involved in transcription remains organized as nucleosomes.

The DNA region being transcribed has been found to be susceptible to DNAase I indicating that the nucleosome organization is displaced from the site of transcription. It may be considered that nucleosomes are displaced when RNA polymerase moves on DNA, and just after transcription, the nucleosomes are formed again.

There are three possibilities regarding the change in chromatin structure during transcription:

(1) The histone octamer undergoes certain changes and remains associated with DNA in the region of transcription.

(2) The histone octamer remains associated with the non-transcribed single strand (the sense strand) of DNA.

(3) The histone octamer is disrupted and the tetramer (H3₂.H4₂) remains associated with DNA, while the H2A. H2B dimers are displaced.

However, it is not clear which of the above possibilities is correct.

Chemical changes in histones:

During the cell cycle, methylation, acetylation and phosphorylation of certain amino acids occur in the histones. These modifications are related to the changes chromatin structure during transcription as well as replication.

Certain amino acids in the histone molecules may react with other substances and their free groups may become methylated acetylated or phosphorylated. Free amino group (-NH₃⁺) of lysine becomes methylated (-CH₃) or acetylated which removes the positive (+) charge of the amino group(Fig. 8.7). Arginine and histidine may also become methylated. Amino acid serine of histone HI becomes phosphorylated at the hydroxyl group (-OH) so that negative (-) charge is added.

The added groups may be removed at a particular stage of cell cycle Acetylation or methylation of core histones occurs during the S phase (DNA synthesis phase) while de-acetylation occurs during G₂. The chromatin structure is affected by acetylation and methylation.

It may also have some relation with the hetero-chromatinization of one of the two X chromosomes of mammalian females. Acetylation of histones causes changes in chromatin structure and the region becomes a “hypersensitive site” to DNAase I. Although, phosphorylation of HI histone occurs during S phase, major phosphorylation events occur after the S phase and before the onset of mitosis.

The enzyme “M phase kinase” is involved in phosphorylation of the HI histone. One phosphate group of ATP is transferred to the serine at the hydroxyl group (Fig. 8.7). The HI phosphorylation is involved in condensation of the chromatin during mitosis. After completion of mitosis, dephosphorylation occurs which is catalyzed by the enzyme “phosphatase”.