Abstract: Disclosed herein are fusion proteins for the targeted activation of genes as well as compositions and methods and DMA Targeting Systems comprising the same. The fusion protein may include at least one first polypeptide domain and at least one second polypeptide domain. The first polypeptide domain includes a DMA binding protein, such as a zinc finger protein, a TALE, or a Cas protein, that targets the fusion protein for binding to a specific DNA sequence. The second polypeptide domain includes a modulator of chromatin structure. The fusion protein may further include a third polypeptide domain, the third polypeptide domain including a transcriptional activator domain.