When thinking about this question, one aspect that comes to mind is the number of these two enzymes. There are 9 different histone acetyltransferases (HATs) in cells, whereas histone deacetylases (HDACs) are twice as many, totaling 18. This higher number of HDACs may provide enhanced specificity, allowing for more targeted regulation of protein functions and, ultimately, more precise targeting of specific diseases, and this is why scientists are focusing more on HDAC inhibition than HAT activation for gene expression. However, the exact reason behind HDAC inhibition over HAT activation is hardly available in the literature. Please let me know your answer. Literature references would be more helpful. Cheers!