H4K8ac

Acetylation of lysine 8 on histone H4

H4K8ac

Lysine acetylation process

H4K8ac refers to the acetylation of the lysine residue at position 8 on the histone H4 protein. This post-translational modification is a key epigenetic marker that plays a significant role in the regulation of gene expression.

Structure and Function

Histone H4 is one of the core histone proteins that form the nucleosome, the basic unit of chromatin structure in eukaryotic cells. The acetylation of lysine residues on histones, such as H4K8, is a reversible modification that affects chromatin dynamics and gene accessibility.

Acetylation neutralizes the positive charge on lysine residues, reducing the interaction between histones and the negatively charged DNA. This process leads to a more relaxed chromatin structure, facilitating access for transcription factors and other DNA-binding proteins, thereby promoting gene expression.

Biological Significance

H4K8ac is associated with active transcription and is often found near the promoters of actively transcribed genes. It is involved in various cellular processes, including DNA repair, replication, and cell cycle progression. The presence of H4K8ac is a marker of open chromatin and is crucial for the regulation of genes involved in cell growth and differentiation.

Regulation

The acetylation of H4K8 is catalyzed by histone acetyltransferases (HATs), which transfer an acetyl group from acetyl-CoA to the lysine residue. Conversely, histone deacetylases (HDACs) remove these acetyl groups, leading to chromatin condensation and transcriptional repression.

The balance between the activities of HATs and HDACs is critical for maintaining proper gene expression patterns and cellular homeostasis. Dysregulation of these enzymes can lead to aberrant gene expression and is implicated in various diseases, including cancer.

Clinical Implications

Alterations in H4K8ac levels have been observed in several types of cancer, where they can influence tumor progression and response to therapy. As a result, H4K8ac and the enzymes that regulate its acetylation state are potential targets for therapeutic intervention.

Histone deacetylase inhibitors (HDAC inhibitors) are a class of drugs that can increase acetylation levels, including H4K8ac, and are being explored as treatments for cancer and other diseases characterized by epigenetic dysregulation.

Related Pages

• Histone acetylation
• Epigenetics
• Chromatin
• Histone deacetylase
• Histone acetyltransferase