H4K91ac

Acetylation of lysine 91 on histone H4

H4K91ac refers to the acetylation of the lysine residue at position 91 on the histone protein H4. This post-translational modification plays a crucial role in the regulation of chromatin structure and function, impacting gene expression, DNA repair, and cell cycle progression.

Histone H4 and its role

Lysine acetylation process

Histone H4 is one of the core histone proteins that form the nucleosome, the fundamental unit of chromatin. Each nucleosome consists of a histone octamer, which includes two molecules each of histone H2A, histone H2B, histone H3, and histone H4, around which approximately 147 base pairs of DNA are wrapped. The N-terminal tail of histone H4 is subject to various post-translational modifications, including acetylation, methylation, and phosphorylation, which influence chromatin dynamics and gene regulation.

Acetylation of lysine 91

Lysine 91 on histone H4 is located within the globular domain of the protein, distinguishing it from many other acetylation sites that are typically found on the N-terminal tail. The acetylation of H4K91 is catalyzed by histone acetyltransferases (HATs), which transfer an acetyl group from acetyl-CoA to the ε-amino group of the lysine residue. This modification neutralizes the positive charge of lysine, reducing the interaction between histone H4 and the negatively charged DNA, thereby facilitating a more open chromatin structure.

Functional significance

H4K91ac is associated with several critical cellular processes:

• Gene expression: The acetylation of H4K91 is linked to transcriptional activation. By loosening the chromatin structure, H4K91ac allows transcription factors and other regulatory proteins to access DNA more easily, promoting the transcription of specific genes.

• DNA repair: H4K91ac is involved in the DNA damage response. It is thought to facilitate the recruitment of DNA repair proteins to sites of damage, thereby enhancing the efficiency of repair mechanisms such as homologous recombination and non-homologous end joining.

• Cell cycle progression: The modification of H4K91 is also implicated in the regulation of the cell cycle. It may play a role in the proper segregation of chromosomes during mitosis and meiosis.

Regulation of H4K91ac

The levels of H4K91ac are tightly regulated by the opposing activities of histone acetyltransferases and histone deacetylases (HDACs). Dysregulation of these enzymes can lead to aberrant acetylation patterns, contributing to the development of various diseases, including cancer.

Related pages

• Histone acetylation
• Chromatin remodeling
• Epigenetics
• Histone code