HDAC 复合物调节 CREB 介导的转录-猫眼课题宝

HDAC 复合物调节 CREB 介导的转录

批准号：

6488490

负责人：

Michael Dale Conkright

金额：

$3.83万

依托单位：

SALK INSTITUTE FOR BIOLOGICAL STUDIES

依托单位国家：

美国

项目类别：

财政年份：

2002

资助国家：

美国

项目状态：

未结题

起止时间：

2002-09-16 至

来源：

https://reporter.nih.gov/project-details/6488490

关键词：

amidohydrolases cAMP response element binding protein chromatin cyclic AMP gene expression genetic transcription immunoprecipitation nucleoproteins nucleosomes phosphorylation polymerase chain reaction postdoctoral investigator protein kinase A protein protein interaction protein structure function stimulant /agonist transcription factor yeast two hybrid system

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英文摘要

The goal of this application is to gain insight into the molecular mechanisms that govern cyclic AMP (cAMP)-mediated gene expression through the phosphorylation-dependent transcription factor, cyclic AMP response element binding-protein (CREB). Specifically, I will be focusing on the role that histone deactylase complexes (HDAC) play in regulating CREB-mediated transcription. My hypothesis is that the association of HDAC complexes with CREB block cellular gene expression by disrupting local chromatin structure and preventing phosphorylation of CREB by PKA in cells exposed to cAMP agonist. To test this hypothesis, I will identify components of the HDAC complexes that interact with CREB. To test whether endogenous HDAC complexes attenuates CREB-mediate transcription, I will also characterize mutant CREB polypeptides that are unable to associate with the HDAC complex. Finally, I will test whether HDAC-mediated deacetylation of promoter-bound nucleosomes hinders phosphorylation by blocking the association of PKA with chromatin.

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