Precise regulation of transcription is essential for proper function, proliferation, and development of eukaryotic cells. However, this process is frequently misregulated in developmental disorders and cancer. Proper understanding of the basic processes underlying gene expression and how they are disrupted are requisite for the development of effective treatments. Unfortunately, the understanding of mechanisms underlying the transcriptional changes during development and tumorigenesis of rare tumors remains lacking. Solitary Fibrous Tumors (SFTs) are a rare tumor type that has a unique intrachromosomal inversion that creates a fusion protein NAB2-STAT6, two transcription regulators. It is unknown how SFTs develop nor how NAB2-STAT6 functions and contributes to their progression. For this thesis, my goal was to investigate how transcription is dysregulated in SFTs. In the first chapter, I establish that NAB2-STAT6 activates an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors. I demonstrate that NAB2-STAT6 localizes to EGR1 targets, recruits transcriptional activators, and increases their expression and chromatin accessibility. I show that SFT’s gene signature closely resembles that of neuroendocrine tumors that have increased IGF2 signaling, an EGR1 target, and the most upregulated gene in SFTs. In the second chapter, I show that INTS10 a subunit of the essential transcriptional regulatory Integrator complex regulates enhancer activation during neuronal differentiation. We demonstrate that INTS10 is a member of the enhancer module of Integrator that stabilizes the binding of SOX2, an essential developmental transcription factor. These data demonstrate a novel function for a submodule of Integrator that links enhancers to promoters essential to drive early developmental processes. In the third chapter, I develop an improved technique to measure nascent RNA transcription, the fraction of RNA that is being actively synthesized thus reflecting the activity of RNA polymerases. Our technique, fastGRO-seq, is more reliable and quick, produces more complete and extensive coverage, and can be done with as little as half a million cells. Altogether, this thesis demonstrates that NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in SFTs, a submodule of Integrator stabilizes active enhancers during neuronal differentiation, and fastGRO is an improved technique to measure nascent RNA transcription.