HISTONE ACETYLTRANSFERASE AND TRANSCRIPTIONAL REGULATION

描述（来自申请人摘要的逐字记录）：组蛋白 乙酰转移酶是高度保守的蛋白质，其中许多发挥着关键作用 调节转录的作用。组蛋白突变或失调 乙酰化可导致恶性肿瘤、发育缺陷和病毒感染。 发病机制然而，人们对转录是如何被理解的知之甚少。 在高度乙酰化的染色质区域内增强。发生了几 提出的假说来解释基因被激活的机制， 组蛋白乙酰转移酶。为了更好地理解这些机制， 研究者将使用芽殖酵母酿酒酵母Gcn 5 p蛋白 作为一个模型来测试以下假设：1）一个或多个早期步骤 Gcn 5 p的酶促作用促进了转录激活。（二） GCN 5 β-乙酰化组蛋白尾部结构域可以募集特异性蛋白质到细胞中， 高乙酰化的染色质区域，其反过来激活转录。第三章 非组蛋白蛋白可以作为Gcn 5 p作用的底物。乙酰化 这些蛋白通过Gcn 5 p在转录中起积极作用。4)两 酵母中Gcn5p-conta.in HAT复合物，佐贺和ADA，可以执行不同的功能。 调节HIS 3表达。具体来说，基因筛查 由于缺乏Gcn 5 p HAT而拯救转录缺陷的抑制子 活性，对于特异性结合乙酰化组蛋白尾部的蛋白质，以及 非组蛋白Gcn 5 p底物。此外，个人角色 ADA和佐贺复合物在HIS 3表达中的作用有待研究 无论是基因上还是生化上

DESCRIPTION (Verbatim from the applicant's abstract): Histone acetyltransferases are well conserved proteins many of which play critical roles in regulating transcription. Mutations or misregulation of histone acetylation can lead to malignancies, developmental defects and viral pathogenesis. It is however poorly understood as to how transcription is enhanced within a hyperacetylated chromatin region. There have been several hypotheses put forth to explain the mechanisms by which genes are activated by histone acetyltransferases. To better understand these mechanisms, the investigator will use the budding yeast Saccharomyces cerevisiae Gcn5p protein as a model to test the following hypotheses: 1) One or more of the early steps of transcriptional activation is facffitated by the Gcn5p enzymatic action. 2) Gcn5p-acetylated histone tail domains may recruit specific proteins to the hyperacetylated chromatin region which in turn activates transcription. 3) Non-histone proteins may serve as substrates for Gcn5p action. Acetylation of these proteins by Gcn5p plays positive roles in transcription. 4) The two Gcn5p-conta.in HAT complexes in yeast, SAGA and ADA, may perform different functions in regulating HIS3 expression. Specifically, genetic screening for suppressors that rescue the transcription defects due to the lack of Gcn5p HAT activity, for proteins that bind specifically the acetylated histone tails, and for non-histone Gcn5p substrates are proposed. Moreover, individual roles played by the ADA and SAGA complexes in HIS3 expression are to be investigated both genetically and biochemically.