Structural Biochemistry/Metabolites

Gene regulation is often affected by variations stemming from the chromatin. A multitude of mechanisms play roles in gene regulation, including “regulation of the core transcription machinery, recruitment of the transcriptional activators or repressors, and altering chromatin structure via post-translational covalent modification of histone proteins.” Yet the most studied and proven mechanism roots from variations of chromatin architecture. Recent research has pointed to a variety of metabolic molecules to be responsible for modulation of genes. Some key metabolic regulators found were: Acetyl-CoA, NAD+, SAM and alpha-KG.

In a landmark study by Kaochar et al., acetylation was found to play a major role in histone modifications, which ultimately leads to gene transcription.

History

In 1964, Allfrey et al. found that the acetylation of the histone tails facilitated access to DNA for transcription by neutralizing the positive charge of lysine side chains. This is due to the fact that many transcription factors interact directly with the acetylated lysines. A significant correlation was found between the ability of a protein to acetylate histones and activate transcription.

Mechanism

The wide range of post-translational modifications of histone proteins allow chromatins to take on a variety of structures. This, in turn, contributes to the cell’s ability to control gene expression.