DNA methylation (DNAme), is an epigenetic modification that involves the addition of a methyl group to the 5th carbon of cytosine and preferentially occurs in a CpG dinucleotide context. In general, the vast majority of CpGs (>80%) are methylated in vertebrate genomes. While global DNAme levels do not change significantly in differentiated cells, DNAme at key regulatory elements such as promoters, enhancers and splice sites are shown to change dynamically and these changes are correlated with transcriptional regulation. Many of these regulatory sites are bound by transcription factors (TF), which are implicated to be methylation sensitive, based on previous genome-wide studies and biochemical binding assays. Yet, the impact of induced DNAme deposition upon binding for these methylation-sensitive factors at selected loci is not well understood. Here we show that by employing the cleavage-deficient CRISPR/Cas9 system (dCas9) combined with the recruitment of a DNA methyltransferase (DNMT3a) we were able to selectively methylate a cohort of CTCF and NRF1 binding sites in the human genome. Further, we tested whether the gain of DNAme at these sites affected the binding of either CTCF or NRF1 and, subsequently, if there was an impact on transcriptional activity. Taken together, this work aims to demonstrate the utility of targeted DNAme in vivo and its potential for directly testing the influence of DNAme on TF binding.