Reversible Histone Acetylation Involved in Transcriptional Regulation of WT1 Gene  

作　　者：Yangguang SHAO Jun LU Cao CHENG Liguo CUI Guoping ZHANG Baiqu HUANG 

机构地区：[1]Key Laboratory of MolecularEpigenetics of Ministry of Education, Institute of Genetics and Cytology Northeast Normal University, Changchun 130024, China, [2]Department of Cell Biology, Key Laboratory of Cell Biology Ministry' of Public Health of China, China Medical University, Shenyang 110001, China

出　　处：《Acta Biochimica et Biophysica Sinica》2007年第12期931-938,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by. the grants from the National Basic Research Project of China （No. 2005CB522404） and the National Natural Science Foundation of China （No. 30571698） We thank Drs. Joan BOYES, Paul M. LIEBERMAN, Richard M. POPE, Odd S. GABRIELSEN, Thierry ROGER, Mary TZUKERMAN, and Edward SETO for providing plasmid constructs.

摘　　要：To validate the involvement of reversible histone acetylation in the transcriptional regulation of human Wilms＇ tumor 1 gene （WT1）, we analyzed the roles of histone deacetylases （HDACs） and histone acetyltransferase in this epigenetic process. Of the six HDACs （HDAC 1-6） examined, HDAC4 and HDAC5 were found to have significant repressing effects on the activity of the WT1 reporter gene, as revealed by luciferase reporter assays and quantitative real-time reverse transcription-polymerase chain reaction assays. Luciferase reporter assays showed that the histone acetyltransferase p300 was able to counteract the HDAC4/HDACS-mediated repression and that p300/CBP synergized with transcription factors Spl, c-Myb, and Ets-1 in activation of the WT1 reporter. Chromatin immunoprecipitation experiments showed that p300 promotes the acetylation level of histone H3 at the WT1 intronic enhancer. Based on these data, we proposed a hypothetical model for the involvement of reversible histone acetylation in transcriptional regulation of the WT1 gene. This study provides further insight into the mechanisms of transcriptional regulation of the WT1 gene and WTl-associated diseases treatment.To validate the involvement of reversible histone acetylation in the transcriptional regulation of human Wilms＇ tumor 1 gene （WT1）, we analyzed the roles of histone deacetylases （HDACs） and histone acetyltransferase in this epigenetic process. Of the six HDACs （HDAC 1-6） examined, HDAC4 and HDAC5 were found to have significant repressing effects on the activity of the WT1 reporter gene, as revealed by luciferase reporter assays and quantitative real-time reverse transcription-polymerase chain reaction assays. Luciferase reporter assays showed that the histone acetyltransferase p300 was able to counteract the HDAC4/HDACS-mediated repression and that p300/CBP synergized with transcription factors Spl, c-Myb, and Ets-1 in activation of the WT1 reporter. Chromatin immunoprecipitation experiments showed that p300 promotes the acetylation level of histone H3 at the WT1 intronic enhancer. Based on these data, we proposed a hypothetical model for the involvement of reversible histone acetylation in transcriptional regulation of the WT1 gene. This study provides further insight into the mechanisms of transcriptional regulation of the WT1 gene and WTl-associated diseases treatment.

关 键 词：histone acetylation WT1 HDAC P300/CBP transcriptional regulation 

分 类 号：Q51[生物学—生物化学]