The code of life is more than a sequence of A’s, C’s, T’s, and G’s. Heart cells in the human body contain the same DNA as skin cells in the foot, yet these two cell types behave in radically different ways. Both contain the DNA for every one of over 20,000 human genes but express only the ones needed for their own form and function. These differences are due to epigenetic processes. Epigenetics refers to any regulation of gene expression that is not based on the sequence of bases in DNA. DNA methylation (the heritable modification of cytosine groups by covalent addition of methyl groups) is one of the most important examples of epigenetic modification. DNA methylation governs critical cellular processes, and hypomethylation in certain regions of the genome can cause myriad diseases including neurodevelopmental disorders, immunodeficiency disorders, and cancer. Currently, there are no effective methods to target methylation to precise regions of the genome, and no simple or inexpensive assays to determine the regions which have been methylated. These problems are compounded by the fact that DNA methylation is almost always studied in mammalian systems with high background methylation activity, resulting in noisy or uninterpretable data. By virtue of its emphasis on the isolation and testing of biological networks in engineered systems with reduced complexity, synthetic biology offers the promise of developing an understanding of phenomena difficult to study in their native environments. It is thus an ideal forum for epigenetic studies, additionally, E. coli does not naturally methylate its DNA in the same way that mammalian systems do, making it a noiseless system to study DNA methylation. We thus sought to adopt a synthetic biology approach to accelerate the development of targeted methylases. Such targeted methylases could be used to tune biological circuitry in synthetic systems, or eventually used to develop targeted methylation therapies. We created a toolbox to enable researchers to engineer the epigenome, it consists of three elements: an economic, quick, noiseless assay for targeted methylation, novel methylases currently being tested for targeting specificity, and software to enable quick screening of these selective enzymes. We characterized our engineered enzymes using our newly developed assay, and analyzed the data using our software. This process was developed into a simple workflow which is inexpensive, open source, and operates in a noiseless environment. Looking towards the future, we are engineering an enzyme that has the potential to mediate transcription in bacterial systems in a methylation sensitive way; our goal is to create an orthogonal, methylation dependent, modular transcriptional silencer in E. coli. We invite you to go on a journey and experience the potential of transcriptional silencing, Penn iGEM is making the impossible a reality.