Histone Methyltransferases

Definition

Histone methyltransferases are enzymes that catalyze the addition of methyl groups to specific amino acids on histone proteins, which plays a critical role in regulating chromatin structure and gene expression. By modifying histones, these enzymes influence the accessibility of DNA to transcription machinery, impacting whether genes are turned on or off. Their actions can lead to either activation or repression of transcription, depending on the specific context and type of methylation involved.

5 Must Know Facts For Your Next Test

1. Histone methyltransferases specifically target lysine and arginine residues on histones, with different methylation patterns leading to distinct transcriptional outcomes.
2. There are two main types of histone methylation: mono-, di-, and tri-methylation, with tri-methylation often being associated with transcriptional activation while others can lead to repression.
3. These enzymes work in conjunction with demethylases, which remove methyl groups, creating a dynamic balance in the regulation of gene expression.
4. Histone methylation can serve as a signal for recruitment of other proteins, such as transcriptional co-activators or repressors, further influencing gene activity.
5. Mutations or dysregulation of histone methyltransferases have been linked to various diseases, including cancer, making them important targets for therapeutic research.

Review Questions

• How do histone methyltransferases influence gene expression through their enzymatic activity?
  • Histone methyltransferases modify histone proteins by adding methyl groups to specific residues. This modification alters chromatin structure, impacting the accessibility of DNA for transcription. Depending on the type and location of the methylation, these enzymes can either promote or inhibit the transcription of genes, demonstrating their crucial role in the regulation of gene expression.
• Compare and contrast histone methylation with histone acetylation in terms of their effects on transcription regulation.
  • Histone methylation and histone acetylation are both important post-translational modifications that affect transcription regulation but do so through different mechanisms. Methylation can either activate or repress transcription depending on the specific context and residue modified, while acetylation is generally associated with increased gene expression. Acetylation neutralizes the positive charge on lysines, reducing histone-DNA interactions and promoting a more open chromatin structure, whereas methylation can recruit different regulatory proteins that either enhance or inhibit access to transcription machinery.
• Evaluate the implications of dysregulation of histone methyltransferases in disease states such as cancer.
  • Dysregulation of histone methyltransferases can lead to abnormal patterns of gene expression that contribute to disease states like cancer. For instance, overactive methyltransferases may silence tumor suppressor genes or activate oncogenes through inappropriate methylation patterns. This disruption can lead to uncontrolled cell growth and tumor progression. Understanding these alterations provides insights into potential therapeutic strategies aimed at correcting these epigenetic modifications, making histone methyltransferases key players in cancer research.

Related terms

Chromatin Remodeling: The process by which the structure of chromatin is altered to either expose or hide certain genes, allowing for regulation of gene expression.

Histone Acetylation: A type of post-translational modification where acetyl groups are added to histones, typically associated with gene activation and increased transcriptional activity.

Transcription Factors: Proteins that bind to specific DNA sequences and regulate the transcription of genetic information from DNA to messenger RNA.