DNA Packaging and Gene Regulation

DNA in Cells

In a typical eukaryotic cell, there is a significant amount of DNA. If all the DNA from a single cell was stretched out end to end, it would measure approximately one meter in length. Given that a cell's diameter is only a few micrometers, this presents a challenge: how does the cell package such a vast amount of DNA into a limited space?

The Role of Histones

To solve the problem of DNA storage, eukaryotic cells wrap their DNA around proteins known as histones. There are several different types of histones, namely:

  • H2A

  • H2B

  • H3

  • H4

These histones come together to form a structure known as a nucleosome. The DNA wraps around each nucleosome approximately twice. In addition to these core histones, there is a fifth histone type called H1, which is not part of the nucleosome structure but is involved in linking nucleosomes together along the DNA strand.

Charge Interactions Between DNA and Histones

DNA is negatively charged due to its phosphate backbone, while histones are positively charged because they are rich in the amino acids arginine and lysine. It is particularly the lysine residues that play an essential role in gene regulation. Gene transcription can be regulated through chemical modifications such as the addition or removal of methyl or acetyl groups on the lysines of histones. This modification alters the histone's affinity for DNA, influencing whether transcription can occur:

  • Acetylation: Generally promotes transcription by reducing histone-DNA binding, making the DNA more accessible to transcription machinery such as RNA polymerase. This form of chromatin is referred to as euchromatin.

  • Methylation: In contrast, leads to tighter binding between DNA and histones, inhibiting transcription. This form is known as heterochromatin.

Accessibility of Chromatin

Euchromatin is associated with active transcription because it is more accessible to the transcriptional machinery. In contrast, heterochromatin, which is tightly packed and less accessible, is associated with repressed transcription.

To remember the effects of these modifications, one can use the mnemonic:

  • "Histone methylation makes DNA mute" (repressive effect)

  • "Histone acetylation makes DNA active" (activating effect)

It is essential to note that these refer specifically to histone modifications, not direct modifications to the DNA itself.

DNA Methylation and CpG Islands

Cells can also methylate their DNA, particularly at regions known as CpG islands. These islands are characterized by a high frequency of cytosine (C) and guanine (G) nucleotides and are often located near gene promoters. The designation CpG refers to the arrangement where the cytosine is followed by a guanine nucleotide, with the "P" representing the phosphate bond connecting them.

Purpose of DNA Methylation

Methylation of CpG islands has significant implications for gene expression. This process is another mechanism that cells use to repress transcription. If a cell determines that it will not need to express a particular gene for a certain period, or possibly ever again, it may methylate the CpG islands in the gene's promoter region. This action effectively silences the gene and ensures that it is not transcribed inadvertently.

Flash Quiz

As a part of the learning reinforcement strategy, the following question is posed:
What effect does methylation of CpG islands have on transcription?
Answer: Methylation represses transcription. Additionally, it is important to note that methylation of histone proteins generally represses transcription as they contribute to making the chromatin heterochromatic rather than euchromatic.