Histone acetyltransferase p300 promotes the activation of human WT1 promoter and intronic enhancer.
The Wilms' tumor gene-1 (WT1) encodes a zinc finger protein involved in gene regulation during kidney, gonad, and heart development. In addition to its promoter, a 258 bp intronic enhancer is required for tissue-specific expression of WT1 gene. p300 is a histone acetyltransferase (HAT) and exerts essential functions in gene regulation. Here, we show that p300 increased the expression of endogenous WT1 mRNA and promoted the activation of the WT1 promoter and intronic enhancer. The results also revealed that the adenovirus E1A repressed the p300 function, while the p300-binding defective E1A delta 2-36 did not, and p300 HAT activity was important for its function since p300 mutant with the HAT domain deleted partially abrogated its ability to activate the WT1 promoter and intronic enhancer. Furthermore, p300 and c-Myb synergistically activated the expression of WT1 gene. This study revealed that p300 and its HAT activity were involved in regulation of WT1 transcription.
Shao
Yangguang
Y
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Lu
Jun
J
Zhang
Guoping
G
Liu
Chunyan
C
Huang
Baiqu
B
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006066:Gonads / Q000378:metabolism; D006321:Heart / Q000502:physiology; D051548:Histone Acetyltransferases; D006801:Humans; D007438:Introns; D007668:Kidney / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D025721:WT1 Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases