What is the Difference Between DNA Methylation and Histone Acetylation

The key difference between DNA methylation and histone acetylation is that DNA methylation results in methylated DNA bases that lead to gene inactivation, while histone acetylation is a modification of the histone proteins associated with the nucleosome structure.

Epigenetic modifications are modifications that result in gene expression regulation without causing any change to the native sequence of the DNA. In this regard, two main chemical modifications, the DNA methylation and histone modification, take place to cause orientational changes in DNA, leading to activation or inactivation of gene expression.


1. Overview and Key Difference
2. What is DNA Methylation
3. What is Histone Acetylation
4. Similarities – DNA Methylation and Histone Acetylation
5. DNA Methylation vs Histone Acetylation in Tabular Form
6. Summary – DNA Methylation vs Histone Acetylation

What is DNA Methylation?

DNA methylation is a main epigenetic modification that takes place in cells. It alters or regulates gene expression. In this phenomenon, DNA bases are methylated with the help of methyl transferases. The methyl groups are transferred from S-adenosyl methionine. The random methylation of DNA bases leads to the inactivation of gene expression. When methylation of DNA takes place in regulatory regions of the DNA such as the promoter sequences, CpG islands, proximal and distal regulatory elements, these sequences are modified, leading to the loss of function of those regulatory regions. As a result, the transcription factors will not bind as expected, and the inactivation or downregulation of gene expression at the transcriptional level takes place. Furthermore, these DNA modifications also will reduce the affinity of RNA polymerase to remain stable during the process of transcription.

Figure 01: DNA Methylation

DNA methylation or hyper-methylation of DNA regions also lead to genomic imprinting, which is an important process in silencing selected genes as a method of regulating the expression of the genes. Mutations activate DNA methylation in genes. Environmental factors, stress, diet, alcohol, and other exogenous factors also activate DNA methylation. For example, a prolonged dietary pattern containing a high composition of methyl donors may lead to the hyper-activation of DNA methylation while a prolonged dietary pattern constituting very low concentrations of methyl donors may lead to demethylation of DNA.

What is Histone Acetylation?

Histone modification is another type of epigenetic modification that causes gene regulation. There are many different chemical modifications taking place on the different histone proteins associated with nucleosome formation during the chromosomal organization of eukaryotes. These modifications include phosphorylation, acetylation, methylation, glycosylation, and ubiquitination.

Figure 02: Histone Acetylation

Histone acetylation is mediated by acetyl transferase enzymes that acetylate amino acid residues of different histone subunits. The lysine amino acid residues of the histone proteins get readily acetylated. Following acetylation, decondensation takes place, producing a more open structure. This will allow the DNA to be exposed more for the transcriptional activation. This orientational change caused by the decondensation of the nucleosome structure will allow RNA polymerase and the transcription factors to be recruited easily to initiate transcription. In contrast, when histone deacetylation takes place, the nucleosome structure undergoes condensation, which will prevent the activation of transcription.

What are the Similarities Between DNA Methylation and Histone Acetylation?

  • Both are epigenetic modifications that take place to regulate gene expression.
  • Both take place only in eukaryotes.
  • Moreover, chemical modifications as a result of an enzymatic activity take place in both scenarios.
  • Exogenous factors such as environment, stress, diet and alcohol regulate both processes.
  • Both processes will not result in any DNA sequence change.
  • These processes take place in the nucleus.

What is the Difference Between DNA Methylation and Histone Acetylation?

DNA methylation and histone acetylation are both epigenetic modifications. However, while DNA methylation takes place at the DNA level, histone acetylation is a chemical covalent modification taking place in proteins as a post-translational modification of histone proteins. So, this is the key difference between DNA methylation and histone acetylation. DNA methylation inactivates transcription while inhibiting transcription initiation and reducing RNA stability. In contrast, histone acetylation will lead to the decondensation of the nucleosome leading to the activation of transcription.

The below infographic presents the differences between DNA methylation and histone acetylation in tabular form for side by side comparison.

Summary – DNA Methylation vs Histone Acetylation

Epigenetic modifications are essential in bringing much diversity to the gene expression pathway by facilitating regulation in response to environmental fluctuations. DNA methylation and histone acetylation are two main types of epigenetic mechanisms that inactivate and activate gene expression, respectively. While both mechanisms do not change the sequence of DNA, it participates in creating orientational changes of DNA that either promote or inhibit gene expression. DNA methylation results in modifying DNA bases by methylating them. In contrast, histone acetylation is the acetylation of selected amino acid residues, leading to decondensed chromatin. These mechanisms are activated in response to stimuli and play an important role in regulating the expression of a particular gene. Thus, this summarizes the difference between DNA methylation and histone acetylation.