Drosophila TRF2 is a preferential core promoter regulator
| Autor: | Dorit Avrahami, Tirza Doniger, John R. Yates, Scott Anderson, James Thompson, Yonathan Zehavi, Yaron Orenstein, Nemone Muster, Yair Glick, Tamar Juven-Gershon, Ron Shamir, Diana Ideses, Doron Gerber, Hiba Waldman Ben-Asher, Chaim Wachtel, Adi Kedmi |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
biology
General transcription factor Response element Amino Acid Motifs RNA polymerase II E-box Promoter Molecular biology TATA Box Cell Line Drosophila melanogaster Gene Expression Regulation Genetics biology.protein Animals Drosophila Proteins Transcription factor II F Telomeric Repeat Binding Protein 2 Transcription factor II D Transcription factor II A Cells Cultured Developmental Biology Research Paper Protein Binding |
| Popis: | Transcription of protein-coding genes is highly dependent on the RNA polymerase II (Pol II) core promoter. Core promoters, generally defined as the regions that direct transcription initiation, span from −40 to +40 relative to the +1 transcription start site (TSS). Core promoters contain functional subregions (termed core promoter elements or motifs, such as the TATA-box, TFIIB recognition elements [BREu and BREd], initiator [Inr], TCT motif, motif 10 element [MTE], and downstream core promoter element [DPE]) that confer specific properties to the core promoter (for review, see Smale 2001; Smale and Kadonaga 2003; Thomas and Chiang 2006; Deng and Roberts 2007; Heintzman and Ren 2007; Juven-Gershon et al. 2008b; Juven-Gershon and Kadonaga 2010; Kadonaga 2012; Lenhard et al. 2012). A synthetic core promoter (termed the super core promoter [SCP]) that contains a TATA, Inr, MTE, and DPE in a single promoter has been shown to yield high levels of transcription, implying that gene expression levels can be modulated via the core promoter (Juven-Gershon et al. 2006). The set of basal transcription factors has been defined using TATA-dependent promoters (for review, see Thomas and Chiang 2006). Transcription of DPE-dependent genes, however, is fundamentally different from transcription of TATA-dependent genes. First and foremost, the set of basal transcription factors that is necessary to transcribe TATA-dependent promoters in vitro is insufficient to transcribe DPE-dependent promoters (Lewis et al. 2005; Goodrich and Tjian 2010). Moreover, enhancers with a preference for DPE-containing promoters or TATA-containing promoters have been discovered (Ohtsuki et al. 1998; Butler and Kadonaga 2001, 2002; Smale 2001). Furthermore, TBP, which is necessary for TATA-dependent transcription, down-regulates DPE-dependent transcription (Hsu et al. 2008). Additionally, NC2 and MOT1, which are positive regulators of DPE-dependent transcription, act by counteracting TBP, thus relieving its inhibition of DPE transcription (Willy et al. 2000; Hsu et al. 2008; van Werven et al. 2008). DPE-dependent promoters can be transcribed using Drosophila high-salt nuclear extracts (Willy et al. 2000). To identify the factors that support DPE-dependent transcription, we used a biochemical complementation approach and fractionated high-salt nuclear extracts in search of proteins that would support DPE transcription. We discovered that TBP (TATA-box-binding protein)-related factor 2 (TRF2) is enriched in the fractions supporting DPE transcription. Drosophila trf2 encodes two protein isoforms that show similarity to the core domain of TBP: a 632-amino-acid protein (the “short TRF2,” which has been extensively studied) and a 1715-amino-acid protein in which the same short TRF2 sequence is preceded by a long N-terminal domain (Kopytova et al. 2006). We explored the functions of TRF2, which is the TRF with the least similarity to TBP, in transcriptional regulation and discovered that short TRF2 preferentially binds and activates DPE-containing promoters. This study highlights the role of short TRF2 as a preferential core promoter regulator and provides insights into the complexity of transcription initiation. |
| Databáze: | OpenAIRE |
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