IDENTIFICATION AND ANALYSIS OF HAT/COACTIVATOR COMPLEXES

点击翻译按钮获取中文摘要

DESCRIPTION (from the application): In the eukaryotic cell nucleus, DNA is packaged by histones into nucleosomes, the repeating subunits of chromatin. The regulation of gene expression from chromatin requires the concerted action of gene specific activator and repressor proteins, general transcription factors and chromatin modifying activities. These enzymes include histone acetlytransferases (HATs) which acetylate the highly conserved lysine residues within histone tails. HAT activities are often found to be associated with large multiprotein coactivator complexes that contain components with identity or homology to known regulators of transcription. These observations have provided a direct molecular basis for the coupling of histone acetylation and the regulation of transcription. The modification of chromatin by acetylation is postulated to play a central role in the etiology of viral infection and cancer and in mechanism of nuclear hormone receptor action. HAT/coactivator proteins are known to associate with cellular oncoproteins and tumor suppressor proteins and have been described in certain translocations associated with leukemias. The goals of this proposal are to understand the biochemical mechanisms and unique functions of native histone acetyltransferase/coactivator complexes. This proposal focuses on a novel yeast acetyltransferase complex named SLIK (SAGA-Like), related in composition to the conserved SAGA HAT/coactivator activity. The identification of this complex has complicated certain genetic interpretations of Ada, Spt and TAFII protein function previously attributed to SAGA. The primary goals of this proposal include 1. Purification and identification of SLIK components, 2. Characterization of the function of individual complex subunits, and 3. Analysis of promoter and gene specificity of SAGA and SLIK complexes. These studies aim to reveal the potential roles of distinct SAGA forms in different activation pathways.