Reversible histone acetylation involved in transcriptional regulation of WT1 gene.
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 (HDAC1-6) 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/HDAC5-mediated repression and that p300/CBP synergized with transcription factors Sp1, 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 WT1-associated diseases treatment.
Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Yangguang
Y
Shao
Jun
J
Lu
Cao
C
Cheng
Liguo
L
Cui
Guoping
G
Zhang
Baiqu
B
Huang
D000107:Acetylation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D016162:Genes, Wilms Tumor / Q000502:physiology*; D006657:Histones / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008954:Models, Biological; D015533:Transcriptional Activation / Q000502:physiology*; D025721:WT1 Proteins / Q000502:physiology*
D006657:Histones; D025721:WT1 Proteins