Characterization of the tbp-tfiia-containing comlex, tac

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Project objective

EC cells are pluripotent cells that are widely used to study the regulation of gene expression during early developmental stages. EC cells can be induced to differentiate into a variety of cell types by retinoic acid (RA), by aggregate formation and by expression of the adenoviral 12S E1A oncoprotein. The coactivator p300 has been implicated in RA- and E1A-induced differentiation but the factors or activities that are downstream of p300 remained unclear. The Stunnenberg's lab have recently identified a novel basal factor, TAC, and provided firm evidence that TAC is a downstream target and effector of p300 activity. TAC is a stable transcriptional complex between TBP and TFIIA, it lacks classical TAFs, and is present and active in EC but not in differentiated cells. The acetyltransferase activity of p300 is crucial for the formation of TAC. Importantly, expression of p300 in differentiated cells instigated the formation of TAC from endogenous proteins. In this project, I will set out to unravel two aspects of the p300-TAC connection, using a combination of biochemical, cell system and in vivo approaches:(1) The role of p300 in TAC formation.(2) The role of p300 in TAC-mediated transcription. Collectively, these experiments are likely to shed light on the putative role of p300 (CBP) and its downstream effector TAC in differentiation of embryonal cells and to provide clues a to the target genes of TAC as well as to the general mechanism of gene trancription.

Original text from CORDIS.

Participants

• STICHTING KATHOLIEKE UNIVERSITEIT · NIJMEGENCoordinatorNetherlands

Links

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