The mechanisms of epigenetic regulators in the regulation of cilia biogenesis. (A) Epigenetic regulators regulate cilia biogenesis through modifications of α-tubulin. Top panel: α-TAT1 and MEC-17 mediated the acetylation of α-tubulin at K40, which facilitates the incorporation of α-tubulin into axoneme, promoting cilia assembly. Middle panel: HDAC6- and SIRT2-mediated deacetylation of α-tubulin destabilizes the cilia, resulting in cilia disassembly and short cilia. Bottom panel: SMYD2-mediated methylation of α-tubulin at K394 is accumulated at the basal body, but not in the axoneme, which also facilitates cilia disassembly, resulting in shorter cilia. (B) Epigenetic regulators regulate cilia biogenesis by regulating the transcription of ciliary genes. Epigenetic regulators—including EZH2, SMYD2, MLL1, and KDM3A—can regulate the transcription of ciliary genes through modification of histone markers, or by directly binding to the promoters of those genes. For example, KDM3A regulates ciliogenesis by regulating the expression of actin, and by binding to the actin cytoskeleton, creating a responsive “actin gate” that controls the access of IFT proteins to the cilia.