This study aims to overcome the limitations of dCas9-regulator systems commonly used in conventional epigenetic editing approaches by utilizing synthetic biology tools based on epigenetic regulators. However, aberrant regulation of epigenetic regulators can lead to serious side effects such as promoting cancer initiation and progression. To address this issue, this study introduces the tDeg system, which selectively degrades unbound dCas9-regulators that are not complexed with gRNAs, thereby enabling the development of a highly specific synthetic gene regulation module. These findings highlight the potential of this refined epigenetic regulation tool to contribute significantly to cellular therapies for diseases such as cancer.