Histone acetyltransferases

Definition

Histone acetyltransferases (HATs) are enzymes that add acetyl groups to the lysine residues on histone proteins, leading to a more relaxed and accessible chromatin structure. This modification plays a crucial role in eukaryotic transcriptional regulation by influencing gene expression, as acetylation typically promotes transcriptional activation by facilitating the binding of transcription factors and other regulatory proteins to DNA.

5 Must Know Facts For Your Next Test

1. HATs are part of larger multi-protein complexes that can have various co-factors, including other enzymes that promote or inhibit transcription.
2. Acetylation by HATs neutralizes the positive charge on lysine residues, reducing the interaction between histones and negatively charged DNA, thereby loosening chromatin structure.
3. HATs can be categorized into different families based on their structural and functional characteristics, including GNAT and p300/CBP families.
4. The activity of HATs is tightly regulated by various signaling pathways, ensuring that gene expression can respond to cellular conditions and stimuli.
5. Defects in HAT activity have been linked to various diseases, including cancer, where abnormal gene expression patterns can arise from altered histone modifications.

Review Questions

• How do histone acetyltransferases influence chromatin structure and gene expression?
  • Histone acetyltransferases influence chromatin structure by adding acetyl groups to lysine residues on histones, which neutralizes their positive charge. This reduction in charge decreases the affinity between histones and DNA, resulting in a more open chromatin configuration. Consequently, this relaxed state allows for easier access of transcription factors and RNA polymerase to DNA, promoting increased gene expression.
• Compare the roles of histone acetyltransferases and deacetylases in the regulation of gene expression.
  • Histone acetyltransferases (HATs) and deacetylases (HDACs) play opposing roles in gene regulation. HATs add acetyl groups to histones, leading to a more relaxed chromatin structure and promoting transcriptional activation. In contrast, HDACs remove these acetyl groups, resulting in tighter DNA-histone interactions and generally repressing gene expression. This balance between acetylation and deacetylation is crucial for maintaining proper control of gene activity.
• Evaluate how alterations in histone acetyltransferase function can contribute to disease pathology, particularly in cancer.
  • Alterations in histone acetyltransferase function can lead to significant changes in gene expression profiles that are associated with various diseases, especially cancer. For example, overactivity of certain HATs can result in excessive transcription of oncogenes, promoting uncontrolled cell growth. Conversely, underactivity may lead to insufficient expression of tumor suppressor genes. These dysregulations can stem from mutations, aberrant signaling pathways, or changes in co-factor availability affecting HAT activity. Understanding these connections highlights the potential for targeting HATs in therapeutic strategies against cancer.

Related terms

Histones: Proteins around which DNA is wrapped to form nucleosomes, helping to package DNA into a compact structure in the nucleus.

Deacetylases: Enzymes that remove acetyl groups from histones, leading to a tighter DNA-histone interaction and generally resulting in transcriptional repression.

Chromatin remodeling: The dynamic alteration of chromatin structure that allows for the accessibility of DNA, playing a key role in regulating gene expression.