Controlling gene expression is essential to growth, development, and sustained life. A critical control point for regulating gene expression is at the level of transcription. The proper regulation of transcription is essential for maintaining normal pathways of cell growth and differentiation, thereby avoiding the rampant cell proliferation observed in tumors. Transcription of protein encoding genes in eukaryotes is orchestrated by a host of protein factors, including RNA polymerase II, general transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), coactivators, chromatin remodeling factors, and gene-specific transcriptional regulators (activators and repressors). The underlying goal of our work is to uncover molecular mechanisms governing mammalian RNA polymerase II transcription. To this end, we use a combination of biochemistry, molecular biology, and molecular genetics to investigate mechanisms of transcriptional regulation in three lines model systems. Our major research areas are the following; 1) Regulation of RNA Polymerase II by non-coding RNAs 2) Regulation of transcription at the human interleukin-2 gene 3) The mechanisms of the human RNA Polymerase II transcription reaction.