Both histone and DNA methylation are epigenetic changes that are essential for controlling chromatin shape and gene expression. Without changing the underlying DNA sequence, these modifications entail the insertion of methyl groups to particular locations on DNA and histone proteins, respectively.
DNA methylation is the process of adding a methyl group to a DNA molecule’s cytosine base, which commonly takes place at CpG dinucleotides (where C stands for cytosine and G for guanine). DNA methyltransferases are enzymes that catalyze this alteration. DNA methylation is typically linked to transcriptional repression and gene silence. Because methylated DNA is often tightly packed, transcription factors and other proteins required for gene expression have a harder time accessing it.
Numerous biological processes, such as embryonic development, X chromosome inactivation, genomic imprinting, and maintenance of cellular identity, depend on DNA methylation. Several disorders, including cancer, have abnormal DNA methylation patterns.
Histones are proteins that make up chromatin, the intricate framework that houses DNA inside the nucleus. Adding methyl groups to particular amino acid residues on histones, especially lysine and arginine residues, is known as histone
methylation. Histone methylation, unlike DNA methylation, can affect gene expression in a variety of ways depending on the histone residue that is changed and the level of methylation.
Depending on the situation, histone methylation can either promote or repress gene expression. In contrast, trimethylation of histone H3 lysine 9 (H3K9me3) is frequently linked to gene repression. As an illustration, trimethylation of histone H3 lysine 4 (H3K4me3) is linked to active gene transcription.
Histone methylation and DNA methylation are linked and can have an effect on one another. As an illustration, DNA methylation at gene promoters can draw proteins that add restrictive histone modifications, further suppressing gene expression. On the other hand, active histone marks can encourage DNA demethylation, which activates genes.
The creation and preservation of cellular identity, as well as reactions to environmental cues, are all influenced by both DNA and histone methylation. The complex interplay between these epigenetic changes is essential for dynamic and context-specific regulation of gene expression.
33 differences between DNA methylation and histone methylation:
|
S.No. |
Aspect |
DNA Methylation |
Histone Methylation |
|
1 |
Definition |
Addition of a methyl group (CH3) to a DNA molecule. |
Addition of a methyl group (CH3) to histone proteins. |
|
2 |
Molecule modified |
DNA molecules are modified. |
Histone proteins within chromatin are modified. |
|
3 |
Location |
Occurs directly on the DNA molecule. |
Occurs on histone proteins associated with DNA. |
|
4 |
Enzymes involved |
Catalyzed by DNA methyltransferase enzymes. |
Catalyzed by histone methyltransferase enzymes. |
|
5 |
Chemical group added |
Methyl group (CH3) is added to a cytosine base. |
Methyl group (CH3) is added to histone lysine or arginine residues. |
|
6 |
Regulatory role |
Can regulate gene expression by silencing or activating genes. |
Can regulate chromatin structure and gene expression. |
|
7 |
Reversible modification |
Generally considered stable and less reversible. |
Can be reversible, allowing for dynamic regulation. |
|
8 |
Heritability |
Can be inherited through cell division. |
Epigenetic marks can be inherited but are generally more dynamic. |
|
9 |
Epigenetic mechanism |
Major epigenetic modification in mammals. |
A key epigenetic modification affecting chromatin structure. |
|
10 |
Biological function |
Involved in gene regulation, genomic stability, and X-chromosome inactivation. |
Involved in chromatin structure and gene regulation. |
|
11 |
Associated diseases |
Aberrant DNA methylation is linked to cancer and developmental disorders. |
Aberrant histone methylation is linked to cancer and other diseases. |
|
12 |
Binding proteins |
Methyl-CpG binding proteins (e.g., MeCP2) bind to methylated DNA. |
Methyl-lysine binding proteins (e.g., chromodomain proteins) bind to methylated histones. |
|
13 |
CpG islands |
Often occurs at CpG dinucleotide sites, forming CpG islands. |
Occurs at specific lysine or arginine residues on histones. |
|
14 |
Influence on chromatin |
Can influence chromatin structure indirectly by recruiting chromatin remodelers. |
Directly affects chromatin structure by altering histone charge and interactions. |
|
15 |
Mechanism of repression |
Represses gene expression by preventing transcription factor binding. |
Can repress or activate gene expression, depending on the context. |
|
16 |
Relationship to imprinting |
Essential for parental imprinting. |
Involved in maintaining parental imprinting. |
|
17 |
Chemical bond involved |
Involves covalent bonding between the methyl group and cytosine. |
Involves covalent bonding between the methyl group and histone amino acids. |
|
18 |
Catalytic activity |
DNA methyltransferases add methyl groups. |
Histone methyltransferases add methyl groups. |
|
19 |
Writer enzymes |
DNMT1, DNMT3A, DNMT3B, etc., are DNA methyltransferases. |
EZH2, DOT1L, and others are histone methyltransferases. |
|
20 |
Eraser enzymes |
DNA demethylases (e.g., TET enzymes) remove methyl groups. |
Histone demethylases (e.g., LSD1, KDM5A) remove methyl groups. |
|
21 |
Functional impact |
Methylation often leads to gene repression. |
Methylation can lead to gene activation or repression, depending on context. |
|
22 |
Histone code hypothesis |
Does not contribute to the histone code hypothesis. |
Integral part of the histone code hypothesis. |
|
23 |
Gene silencing |
Major mechanism for gene silencing. |
One of multiple mechanisms for gene silencing. |
|
24 |
Influence on chromatin remodelers |
Indirectly influences chromatin remodelers. |
Directly affects interactions with chromatin remodelers. |
|
25 |
Role in X-inactivation |
Critical for X-chromosome inactivation in females. |
Not directly involved in X-inactivation. |
|
26 |
Timing of modification |
Occurs throughout the cell cycle, including replication. |
Can occur during various phases of the cell cycle. |
|
27 |
Maintenance during replication |
DNMT1 helps maintain DNA methylation patterns during DNA replication. |
Maintenance mechanisms are less understood. |
|
28 |
Role in heterochromatin |
Important for the formation of constitutive heterochromatin. |
Plays a role in heterochromatin formation and maintenance. |
|
29 |
Inheritance mechanisms |
Inherited epigenetically through mitosis and meiosis. |
Inherited epigenetically but with some degree of plasticity. |
|
30 |
Transgenerational effects |
Can contribute to transgenerational epigenetic inheritance. |
Can contribute to transgenerational epigenetic inheritance. |
|
31 |
Targets in epigenetic therapy |
DNA methylation inhibitors (e.g., 5-azacytidine) are used in therapy. |
Histone methyltransferase inhibitors are under investigation for therapy. |
|
32 |
Role in genomic stability |
Essential for maintaining genomic stability. |
Implicated in maintaining genomic stability. |
|
33 |
Target of epigenetic drugs |
Targeted by DNA demethylating drugs. |
Targeted by histone demethylating drugs. |
Frequently Asked Questions (FAQs)
1. How does gene expression depend on DNA methylation?
DNA methylation can prevent transcription factors and other proteins from attaching to the gene’s promoter region, preventing the production of the gene. Additionally, it can attract proteins that alter the structure of chromatin, creating a repressive chromatin environment that inhibits gene transcription.
2.What enzymes are involved in the methylation of DNA?
DNA methyltransferases (DNMTs), including DNMT1, DNMT3A, and DNMT3B, are principally responsible for catalyzing DNA methylation. While DNMT3A and DNMT3B are in charge of de novo DNA methylation, DNMT1 is important in preserving current DNA methylation patterns during DNA replication.
3. How does gene expression depend on histone methylation?
Depending on the particular histone residue being methylated and the context of other histone alterations, histone methylation can result in either gene activation or repression. For instance, H3K4 methylation is typically linked to gene activation, whereas H3K9 and H3K27 methylation is frequently associated with gene repression.
4. What part does DNA methylation play in health and disease?
DNA methylation is essential for many biological processes, such as cellular differentiation, gene control, and growth. Numerous disorders, including cancer, are characterized by abnormal DNA methylation patterns. In cancer, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes can promote tumor growth.
5.How do histone methylation and DNA methylation interact?
Histone methylation and DNA methylation are linked epigenetic processes that control gene expression. Together, they can create consistent patterns of gene expression. Inducing restrictive histone modifications, for instance, can be induced by DNA methylation at promoter regions, which can attract proteins and further silence gene expression.
