Our laboratory is interested in the transcriptional mechanisms responsible for rapid induction of mammalian genes. We are currently focused on the control of RNAPII elongation at the HIV-1 promoter by the HIV-1 Tat protein, which acts through an RNA element to recruit the host cell P-TEFb (CycT1:CDK9) elongation factor. We recently found that an alternative splicing factor, SKIP, also regulates RNAPII transcription elongation. SKIP associates with P-TEFb and is required for Tat activation, and current studies are seeking to identify how SKIP and associated factors control transcription elongation at HIV-1 and cellular genes. We are also examining how non-coding regulatory RNAs control transcription elongation and P-TEFb activity, and how transcription elongation is coupled to specific chromatin modifications, including H3K4 methylation and H3K36 methylation in vivo. These studies should help us better understand the intricate links between transcription elongation, nucleosome methylation, and RNA processing and export in human cells. Another area of interest is the mechanisms that regulate Wnt and Notch signaling in human colon cancers. We recently showed that the Wnt co-activator, beta-catenin, interacts with factors required for H3K4 methylation of target genes, and that the APC tumor suppressor functions to down-regulate beta-catenin transcription at target genes. Recent studies indicate that Notch transcription is strongly regulated at the level of transcription elongation through P-TEFb and SKIP, and are studying how these factors are recruited and function in response to Notch signaling.