Function of diverse transcriptional coactivators in animal cells
Professor Robert G. Roeder
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University
429th Medical Research Institute Seminar
16:30, 1 April 2010
Memorial Auditorium, Tokyo Medical and Dental University
Cells in various environments are getting different signals that reach nuclear DNA then activate transcriptions of corresponding genes. Transcription itself is done by general transcription machinery, but the gene specificity requires some other factors through which the specificity is determined. Having ability to bridge between the enhancer specific complex and the transcription machinery, transcriptional coactivators are a group of factors that regulate the signal-specific transcriptional outcomes.
There are two classes of the coactivators; direct and indirect. Direct ones mediate signal transduction between a receptor and the transcription machinery. MED1 is a member of complex relating PPARgamma2 mediated adipogenesis. MED1-/- is embryonic lethal and fibroblasts derived from the MED1-/- show a deficiency of the adipocyte differentiation. The LXXLL motif is appeared to be essential for the mediator activity.
Indirect ones regulate gene specificity through mainly modifications of chromatin structure, especially histone modification status. p53 has several target genes that require histone modifications on certain sites for the gene activation. PRMT1, p300 and CARM1 are shown to methylate and acetylate components of core histone (H3Me, H3Ac and H4Ac, and H3Me respectively). Even though the sequential acts of these coactivators are essential for p53-dependent gene activation, bona fide nature of the modification remains unsolved.
