On a roll for new TRF targets
TL;DR: In this issue of Genes & Development, Isogai et al. (2007a) report that the TATA-less histone H1 promoter is regulated by TRF2, which provides a possible mechanism for earlier observations linking TRF3 with chromatin structure and helps to establish Drosophila TRF 2 as a broadly used core-promoter factor.
Abstract: In the early 1990s, one of us wrote in these pages a review entitled “TBP, a universal transcription factor?” (Hernandez 1993). At the time, it had become clear that the TATA-box-binding protein TBP was not a transcription factor exclusively involved in transcription from RNA polymerase II (pol II) promoters as had been thought before, but rather a factor involved in transcription by all three main types of eukaryotic nuclear RNA polymerases. In retrospect, however, the question mark at the end of the title was a wise touch! Indeed, shortly thereafter, the first TBP-related factor, TRF1, was described (Crowley et al. 1993). Since then, two more TRFs have been discovered (for review, see Berk 2000; Davidson 2003; Hochheimer and Tjian 2003), and it was found that some genes dispense with TBP and TRFs altogether (Wieczorek et al. 1998). This “expansion” of TBP into a TBP family of proteins begs the question of which promoters are targeted by which TBP family member. In this issue of Genes & Development, Isogai et al. (2007a) report that the TATA-less histone H1 promoter is regulated by TRF2. This provides a possible mechanism for earlier observations linking TRF2 with chromatin structure (Martianov et al. 2002; Kopytova et al. 2006). Furthermore, the identification by Isogai et al. (2007a) of a large number of TRF2-bound sites in the Drosophila genome helps to establish Drosophila TRF2 as a broadly used core-promoter factor. Among the three classes of TBP-related factors described so far, TRF2—also called TBP-like protein (TLP) or TBP-like factor (TLF)—is the only one to be widely present in metazoans (Ohbayashi et al. 1999; Kaltenbach et al. 2000; Veenstra et al. 2000). TRF1 has been found only in Drosophila and Anopheles (Crowley et al. 1993; Isogai et al. 2007b), and TRF3 is restricted to vertebrates (Persengiev et al. 2003). All three proteins contain a core domain related to the TBP C-terminal core domain, and some also contain variable Nand C-terminal domains.
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TL;DR: The findings suggest that the core promoter and basal transcription factors are important yet mostly unexplored components in the regulation of gene expression.
Abstract: The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional regulatory element. There are two main strategies for transcription initiation - focused and dispersed initiation. In focused initiation, transcription starts from a single nucleotide or within a cluster of several nucleotides, whereas in dispersed initiation, there are several weak transcription start sites over a broad region of about 50 to 100 nucleotides. Focused initiation is the predominant means of transcription in simpler organisms, whereas dispersed initiation is observed in approximately two-thirds of vertebrate genes. Regulated genes tend to have focused promoters, and constitutive genes typically have dispersed promoters. Hence, in vertebrates, focused promoters are used in a small but biologically important fraction of genes. The properties of focused core promoters are dependent upon the presence or absence of sequence motifs such as the TATA box and DPE. For example, Caudal, a key regulator of the homeotic gene network, preferentially activates transcription from DPE- versus TATA-dependent promoters. The basal transcription factors, which act in conjunction with the core promoter, are another important component in the regulation of gene expression. For instance, upon differentiation of myoblasts to myotubes, the cells undergo a switch from a TFIID-based transcription system to a TRF3-TAF3-based system. These findings suggest that the core promoter and basal transcription factors are important yet mostly unexplored components in the regulation of gene expression.
489 citations
Cites background from "On a roll for new TRF targets"
...This concept is nicely exemplified in studies of the TBP-related factors (TRFs) (for reviews, see: Jones, 2007; Müller et al., 2007; Reina and Hernandez, 2007; Torres-Padilla and Tora, 2007)....
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TL;DR: The core promoter is a sophisticated gateway to transcription that determines which signals will lead to transcription initiation and may contain many different sequence motifs that specify different mechanisms of transcription and responses to enhancers.
Abstract: The RNA polymerase II core promoter is generally defined to be the sequence that directs the initiation of transcription. This simple definition belies a diverse and complex transcriptional module. There are two major types of core promoters - focused and dispersed. Focused promoters contain either a single transcription start site or a distinct cluster of start sites over several nucleotides, whereas dispersed promoters contain several start sites over 50-100 nucleotides and are typically found in CpG islands in vertebrates. Focused promoters are more ancient and widespread throughout nature than dispersed promoters; however, in vertebrates, dispersed promoters are more common than focused promoters. In addition, core promoters may contain many different sequence motifs, such as the TATA box, BRE, Inr, MTE, DPE, DCE, and XCPE1, that specify different mechanisms of transcription and responses to enhancers. Thus, the core promoter is a sophisticated gateway to transcription that determines which signals will lead to transcription initiation.
380 citations
TL;DR: A simple model in which basal transcription factors sequentially assembled with RNA Polymerase II to generate a preinitiation complex (PIC) indicates that PIC composition is not universal, but promoter-dependent.
Abstract: In vitro experiments led to a simple model in which basal transcription factors sequentially assembled with RNA Polymerase II to generate a preinitiation complex (PIC). Emerging evidence indicates that PIC composition is not universal, but promoter-dependent. Active promoters are occupied by a mixed population of complexes, including regulatory factors such as NC2, Mot1, Mediator, and TFIIS. Recent studies are expanding our understanding of the roles of these factors, demonstrating that their functions are both broader and more context dependent than previously realized.
193 citations
Cites background from "On a roll for new TRF targets"
...The other subunits of TFIID (the TBP-associated factors or TAFs) appear to interact with INR and DPEs....
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...Leurent C, Sanders S, Ruhlmann C, Mallouh V, Weil PA, Kirschner DB, Tora L, Schultz P: Mapping histone fold TAFs within yeast TFIID....
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...In higher eukaryotes, there are multiple genes encoding TBP-related factors (TRFs) and variant TAFs [1,7]....
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TL;DR: A broad spectrum of studies that highlight the importance of the core promoter and its pivotal role in the regulation of metazoan gene expression are reviewed and future research directions and challenges are suggested.
Abstract: The identities of different cells and tissues in multicellular organisms are determined by tightly controlled transcriptional programs that enable accurate gene expression. The mechanisms that regulate gene expression comprise diverse multiplayer molecular circuits of multiple dedicated components. The RNA polymerase II (Pol II) core promoter establishes the center of this spatiotemporally orchestrated molecular machine. Here, we discuss transcription initiation, diversity in core promoter composition, interactions of the basal transcription machinery with the core promoter, enhancer-promoter specificity, core promoter-preferential activation, enhancer RNAs, Pol II pausing, transcription termination, Pol II recycling and translation. We further discuss recent findings indicating that promoters and enhancers share similar features and may not substantially differ from each other, as previously assumed. Taken together, we review a broad spectrum of studies that highlight the importance of the core promoter and its pivotal role in the regulation of metazoan gene expression and suggest future research directions and challenges.
140 citations
Cites background from "On a roll for new TRF targets"
...which is essential for interaction with the TATA box (reviewed in [121-123, 144-146]....
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TL;DR: The proposed models of transcription initiation by alternative initiation complexes in distinct stages of developmental specialization during vertebrate ontogeny are summarized.
Abstract: The traditional model of transcription initiation nucleated by the TFIID complex has suffered significant erosion in the last decade. The discovery of cell-specific paralogs of TFIID subunits and a variety of complexes that replace TFIID in transcription initiation of protein coding genes have been paralleled by the description of diverse core promoter sequences. These observations suggest an additional level of regulation of developmental and tissue-specific gene expression at the core promoter level. Recent work suggests that this regulation may function through specific roles of distinct TBP-type factors and TBP-associated factors (TAFs), however the picture emerging is still far from complete. Here we summarize the proposed models of transcription initiation by alternative initiation complexes in distinct stages of developmental specialization during vertebrate ontogeny.
83 citations
References
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TL;DR: Analyzing gene-expression patterns by in situ hybridization to whole-mount embryos provides an extremely rich dataset that can be used to identify genes involved in developmental processes that have been missed by traditional genetic analysis.
Abstract: Background: Cell-fate specification and tissue differentiation during development are largely achieved by the regulation of gene transcription. Results: As a first step to creating a comprehensive atlas of gene-expression patterns during Drosophila embryogenesis, we examined 2,179 genes by in situ hybridization to fixed Drosophila embryos. Of the genes assayed, 63.7% displayed dynamic expression patterns that were documented with 25,690 digital photomicrographs of individual embryos. The photomicrographs were annotated using controlled vocabularies for anatomical structures that are organized into a developmental hierarchy. We also generated a detailed time course of gene expression during embryogenesis using microarrays to provide an independent corroboration of the in situ hybridization results. All image, annotation and microarray data are stored in publicly available database. We found that the RNA transcripts of about 1% of genes show clear subcellular localization. Nearly all the annotated expression patterns are distinct. We present an approach for organizing the data by hierarchical clustering of annotation terms that allows us to group tissues that express similar sets of genes as well as genes displaying similar expression patterns. Conclusions: Analyzing gene-expression patterns by in situ hybridization to whole-mount embryos provides an extremely rich dataset that can be used to identify genes involved in developmental processes that have been missed by traditional genetic analysis. Systematic analysis of rigorously annotated patterns of gene expression will complement and extend the types of analyses carried out using expression microarrays.
740 citations
"On a roll for new TRF targets" refers background in this paper
...Interestingly, a computational analysis identified the DRE as one of the prevalent core-promoter motifs in the Drosophila genome, raising the possibility that the TRF2/DREF-containing complex controls a large group of promoters (Ohler et al. 2002; Tomancak et al. 2002)....
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TL;DR: A key step in retrieving the information stored in the complex genomes of eukaryotes involves the identification of transcription units and, more specifically, the recognition of promoter sequences by RNA polymerase.
Abstract: A key step in retrieving the information stored in the complex genomes of eukaryotes involves the identification of transcription units and, more specifically, the recognition of promoter sequences by RNA polymerase. In eukaryotes, the task of recognizing nuclear gene promoters and then transcribing the genes is divided among three highly related enzymes, RNA polymerases I, II, and III. Each of these RNA polymerases is dedicated to the transcription of specific sets of genes, and each depends on accessory factors, the so-called transcription factors, to recognize its cognate promoter sequences.
601 citations
"On a roll for new TRF targets" refers background in this paper
...In Drosophila cells, then, the TFIIIB activity, which is the key factor responsible for pol III recruitment (for a review, see Schramm and Hernandez 2002), contains Brf1 and TRF1, whereas in yeast it contains Brf1 and TBP....
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583 citations
Additional excerpts
...(Hernandez 1993)....
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TL;DR: Results indicate that linker histones can participate in epigenetic regulation of gene expression by contributing to the maintenance or establishment of specific DNA methylation patterns.
Abstract: Linker histone H1 plays an important role in chromatin folding in vitro. To study the role of H1 in vivo, mouse embryonic stem cells null for three H1 genes were derived and were found to have 50% of the normal level of H1. H1 depletion caused dramatic chromatin structure changes, including decreased global nucleosome spacing, reduced local chromatin compaction, and decreases in certain core histone modifications. Surprisingly, however, microarray analysis revealed that expression of only a small number of genes is affected. Many of the affected genes are imprinted or are on the X chromosome and are therefore normally regulated by DNA methylation. Although global DNA methylation is not changed, methylation of specific CpGs within the regulatory regions of some of the H1 regulated genes is reduced. These results indicate that linker histones can participate in epigenetic regulation of gene expression by contributing to the maintenance or establishment of specific DNA methylation patterns.
551 citations
"On a roll for new TRF targets" refers background in this paper
...Indeed, the observation that TRF2 depletion leads to both reduced amounts of histone H1 and altered polytene chromosomes provides further evidence that varying levels of histone H1 can have dramatic effects on chromatin structure (Fan et al. 2005)....
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TL;DR: The author’s views are based on personal experience, research, and interviews conducted at the 2016 USGS workshop on “Biology of infectious disease: Foundations of Natural Selection and Response to infectious disease .”
Abstract: AND PERSPECTIVE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 827 ORGANIZATION OF HISTONE GENES-STRUCTURE OF HISTONE mRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 828 OVERVIEW OF HIS TONE SYNTHESIS IN THE CELL CyCLE . . . . . . . . . . . . . . . . . . . . . . . . 829 TRANSCRIPTIONAL REGULATION . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 832 Higher Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . ... . . . . . . . . 832 Lower Eukaryotes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 841 POSTTRANSCRIPTIONAL REGULATION . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . .... 847 Higher Eukaryotes. . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . . . . . . . . . . . . . . . .. . . . . . . . 847 Lower Eukaryotes . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... . . . . . . . . . . . . . . . . . . 853 MULTIPLE FORMS OF REGULATION MODULATE HISTONE mRNA LEVELS IN THE CELL CyCLE . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . !l55 FUTURE PROSPECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . .. . . . . . . . . . . . . . . . . . ... .. . . . . .. . . . . . . . . . 856
510 citations
"On a roll for new TRF targets" refers background in this paper
...In higher eukaryotes the organization is different in that the histone genes are more dispersed even though some clusters occur, and the number of copies per haploid genome is lower (for review, see Osley 1991)....
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