Acetylation machinery has diverse functions. A subset of target genes may require the presence of both copies of either of the histone acetyltransferases “writers” (CREBBP and EP300). The full complement of histone acetyltransferases may ensure open chromatin and expression from some loci (top, middle). Alternatively, other genes may be dominated by HDACs that favor repressed chromatin (top, sides). However, HDAC8 also plays a role in removing the acetylation mark from cohesins and may also have other roles in cytoplasm. Similarly, CREBBP and EP300 regulate other proteins such as TP53 through acetylation in nucleus and ubiquitination in the cytoplasm. There are also other components that interact with the components of the epigenetic or cohesion machinery, such as RPS6KA3 and ESCO1, that also lead to intellectual disability.
