Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors
| Autor: | Fang Liu, Amit Maity, Nabendu Pore, Melissa L. Dowling, Gary D. Kao, K. Ranh Voong, Mijin Kim |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Sp1 Transcription Factor Cellular differentiation Molecular Sequence Data Repressor Biology Gene Expression Regulation Enzymologic Histone Deacetylases Sp3 transcription factor Consensus Sequence Animals Humans Tissue Distribution Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Gene knockdown Sp1 transcription factor Binding Sites Base Sequence Articles Plicamycin Cell Biology HDAC4 Molecular biology Repressor Proteins Sp3 Transcription Factor Drosophila Chromatin immunoprecipitation HeLa Cells |
| Zdroj: | Molecular Biology of the Cell. 17:585-597 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4. |
| Databáze: | OpenAIRE |
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