What is the effect of increased HDAC activity on transcription?

Increased HDAC (histone deacetylase) activity leads to decreased transcription. HDACs are enzymes that remove acetyl groups from the lysine residues of histone proteins. Acetylation generally results in a more relaxed chromatin structure, allowing transcription machinery to access DNA and initiate transcription. Conversely, when HDAC activity increases, the removal of these acetyl groups leads to a more compacted, closed chromatin conformation. This tighter packing inhibits the access of transcription factors and RNA polymerase to the DNA, thereby reducing transcriptional activity.

As a result, genes that would normally be expressed are silenced when HDAC activity is high, leading to decreased levels of mRNA and, consequently, decreased protein synthesis. This mechanism is fundamental to understanding how epigenetic regulation can control gene expression, influencing cellular functions and developmental processes.