PU.1 and a TTTAAA element in the myeloid Defensin-1 promoter create an operational TATA box that can impose cell specificity onto TFIID function Journal Article
| Authors: | Yaneva, M.; Kippenberger, S.; Wang, N.; Su, Q.; McGarvey, M.; Nazarian, A.; Lacomis, L.; Erdjument-Bromage, H.; Tempst, P. |
| Article Title: | PU.1 and a TTTAAA element in the myeloid Defensin-1 promoter create an operational TATA box that can impose cell specificity onto TFIID function |
| Abstract: | Defensins are major components of a peptide-based, antimicrobial system in human neutrophils. While packed with peptide, circulating cells contain no defensin-1 (def1) transcripts, except in some leukemia patients and in derivative promyelocytic leukemia cell lines. Expression is modulated by serum factors, mediators of inflammation, and kinase activators and inhibitors, but the underlying mechanisms are not fully understood. A minimal def1 promoter drives transcription in HL-60 cells under control of PU.1 and a def1-binding protein ("D1BP"), acting through, respectively, proximal (-22/-19) and distal (-162/-59) GGAA elements. In this study, we identify D1BP, biochemically and functionally, as GA-binding protein (GABP)α/GABPβ. Whereas GABP operates as an essential upstream activator, PU.1 assists the flanking "TTTAAA" element (-327-27), a "weak" but essential TATA box, to bring TBP/TFIID to the transcription start site. PU.1 thus imparts a degree of cell specificity to the minimal promoter and provides a potential link between a number of signaling pathways and TFIID. However, a "strong" TATA box ("TATAAA") eliminates the need for the PU.l binding site and for PU.1, but not for GABP. As GABP is widely expressed, a strong TATA box thus alleviates promyelocytic cell specificity of the def1 promoter. These findings suggest how the myeloid def1 promoter may have evolutionarily acquired its current properties. Copyright © 2006 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; protein expression; leukemia; unclassified drug; human cell; promoter region; proto-oncogene proteins; nonhuman; protein function; animal cell; animals; protein kinase inhibitor; cell line; inflammation; protein binding; evolution; genetic transcription; cell line, tumor; cell specificity; amino acid sequence; molecular sequence data; neutrophil; recombinant proteins; promyelocytic leukemia; base sequence; binding protein; binding site; binding sites; trans-activators; drosophila melanogaster; transcription initiation site; myeloid cells; tata box; proto-oncogene proteins c-ets; promoter regions (genetics); transcription factor pu 1; enzyme activator; 5' flanking region; hl-60 cells; cell strain hl 60; defensin; defensins; transcription factor tfiid; transcription factor iid; defensin binding protein; ga binding protein alpha; ga binding protein beta; dinucleotide repeats; tata-box binding protein |
| Journal Title: | Journal of Immunology |
| Volume: | 176 |
| Issue: | 11 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2006-06-01 |
| Start Page: | 6906 |
| End Page: | 6917 |
| Language: | English |
| PUBMED: | 16709851 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 4 June 2012" - "CODEN: JOIMA" - "Source: Scopus" |
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