In eukaryotic cells, activator and repressor proteins can exploit the mechanisms used to package DNA to help turn genes on and of.

Chromatin structure can be altered by chromatin-remodeling complexes and by enzymes that covalently modify the histone proteins that form the core of the nucleosome. Many gene activators take advantage of these mechanisms by attracting such chromatin-modifying proteins to promoters.

For example, the recruitment of histone acetyltransferases promotes the attachment of acetyl groups to selected lysines in the tail of histone proteins; these acetyl groups themselves attract proteins that promote transcription, including some of the general transcription factors. And the recruitment of chromatin-remodeling complexes makes nearby DNA more accessible. These actions enhance the efficiency of transcription initiation.

In a similar way, gene repressor proteins can modify chromatin in ways that reduce the efficiency of transcription initiation. For example, many repressors attract histone deacetylases—enzymes that remove the acetyl groups from histone tails, thereby reversing the positive effects that acetylation has on transcription initiation.