Histone modification pathways. Histone acetylation is mediated by HAT and deacetylation is catalyzed by the HDAC family. The upper row represents histone acetylation/deacetylation processes mediated by classic HDAC family members, including classes I, II and IV. Histone acetylation causes an open chromatin structure, leading to active transcription, whereas histone deacetylation is always associated with transcriptional repression. The middle row indicates a class III HDAC family member, SIRT1, which deacetylates both histone and protein substrates, resulting in gene silencing in most cases. The lower row represents histone methylation as another important histone modification. Histone methylation is mediated by HMT, and either gene activation or gene repression by histone methylation is dependent upon the particular lysine residue that is modified. HAT, histone acetyltransferase; HDAC, histone deacetylase; HMT, histone methyltransferase. SIRT1, Sirtuin (silent mating type information regulation 2 homolog) 1.