nuclear cgmp-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex核cgmp-dependent通过活动依赖性激酶调节基因表达的招聘守恒的组蛋白脱乙酰酶复杂.pdfVIP

Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex 1 1 1 1 1 1 Yan Hao , Ningyi Xu , Andrew C. Box , Laura Schaefer , Kasthuri Kannan , Ying Zhang , Laurence 1 1 1,2 1 1,3 Florens , Christopher Seidel , Michael P. Washburn , Winfried Wiegraebe , Ho Yi Mak * 1 Stowers Institute for Medical Research, Kansas City, Missouri, United States of America, 2 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America, 3 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America Abstract Elevation of the second messenger cGMP by nitric oxide (NO) activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarr