Tip60 is a cell-type-specific transcriptional regulator.
Tip60 was originally identified as cellular HIV-Tat interacting protein and has been shown to augment Tat-dependent transcription. It has also been shown to interact with various cellular transcription factors and to belong to the nuclear histone acetyltransferase (HAT) family. To further elucidate the function of Tip60 and its HAT domain in transcription regulation, we compared Tip60 activity in HeLa and Jurkat T lymphoma cells. Here we show that Tip60 augments the HIV-1 Tat activity at the HIV-LTR promoter in HeLa but inhibits it in Jurkat cells. Moreover, we isolated two new variants of the Tip60 protein (Tip60Delta1, Tip60Delta2) from Jurkat cells. The Tip60Delta2 variant lacks the entire HAT domain but modulates HIV-1 Tat activity like full-length Tip60. In addition, Tip60 and the transcriptional repressor ZEB (zinc finger E box binding protein) interact specifically in the yeast two-hybrid system and additively inhibit the CD4 enhancer/promoter activity in Jurkat cells. Thus, Tip60 may function as corepressor of the ZEB protein. In summary, these data show that Tip60 functions as a cell-type-specific transcriptional regulator and that the HAT domain is not required for either transcriptional activation or inhibition. This indicates that Tip60 may function by recruiting additional cell-type-specific cofactors.
Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany.
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F
Hlubek
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Löhberg
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J
Meiler
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A
Jung
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Kirchner
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Brabletz
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015704:CD4 Antigens / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D000074443:Lysine Acetyltransferase 5; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015704:CD4 Antigens; D015696:Gene Products, tat; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5