Retinoids are important lipophilic hormones whose actions are mediated through interactions with retinoid receptors (RARs and RXRs). Retinoid receptors function as ligand-regulated transcription factors that control the expression of genes involved in the normal and pathophysiological biology of many organ systems including the mammary glands, reproductive and urinary tracts, and nervous tissue. My research is aimed at defining the molecular mechanisms regulating retinoid-mediated transcription by testing the broad hypothesis that multiple protein complexes are required for retinoid-directed chromatin remodeling and transcription activation. To clarify the factors and interactions that modulate transcription through retinoid receptors, I will use a biochemical system that accurately recreates ligand-, receptor-, and coregulator-dependent transcriptional events with immobilized chromatin templates assembled and transcribed in vitro. This system will be used to identify and characterize factors that interact with retinoid receptors to regulate transcription and facilitate chromatin remodeling. The use of chromatin templates immobilized on paramagnetic beads has the advantage over other biochemical systems in that it will allow purification of complexes that are directly associated with transcriptionally active retinoid-regulated promoters assembled into chromatin. An ameliorated understanding of the signaling pathways involving retinoid-mediated transcription in both normal and cancer cells has great potential to lead to the development of more effective diagnostic, preventative and therapeutic options.
| Acevedo, Mari Luz; Lee, Kathleen C; Stender, Joshua D et al. (2004) Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. Mol Cell 13:725-38 |
| Lee, Kathleen C; Li, Jiwen; Cole, Philip A et al. (2003) Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivators. Mol Endocrinol 17:908-22 |
