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BBA - Gene Regulatory Mechanisms (v.1829, #3-4)
Odd RNA polymerases or the A(B)C of eukaryotic transcription by André Sentenac; Michel Riva (pp. 251-257).
Pioneering studies on eukaryotic transcription were undertaken with the bacterial system in mind. Will the bacterial paradigm apply to eukaryotes? Are there promoter sites scattered in the eukaryotic genome, and sigma-like proteins? Why three forms of RNA polymerase in eukaryotic cells? Why are they structurally so complex, in particular RNA polymerases I and III, compared to the bacterial enzyme? These questions and others that were raised along the way are evoked in this short historical survey of odd RNA polymerases studies, with some emphasis on the contribution of these studies to our global understanding of eukaryotic transcription systems. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Eukaryotic transcription studies: a Russian dolls story ► Old, unanswered questions ► Uncompleted quest for factors and regulators
Keywords: Odd polymerases; Historical perspective
A structural perspective on RNA polymerase I and RNA polymerase III transcription machineries by Alessandro Vannini (pp. 258-264).
RNA polymerase I and III are responsible for the bulk of nuclear transcription in actively growing cells and their activity impacts the cellular biosynthetic capacity. As a consequence, RNA polymerase I and III deregulation has been directly linked to cancer development. The complexity of RNA polymerase I and III transcription apparatuses has hampered their structural characterization. However, in the last decade tremendous progresses have been made, providing insights into the molecular and functional architecture of these multi-subunit transcriptional machineries. Here we summarize the available structural data on RNA polymerase I and III, including specific transcription factors and global regulators. Despite the overall scarcity of detailed structural data, the recent advances in the structural biology of RNA polymerase I and III represent the first step towards a comprehensive understanding of the molecular mechanism underlying RNA polymerase I and III transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols.► A summary of structural data available for Pol I and Pol III transcription machineries ► First insights into the structural architecture of Pol I and Pol III transcription machineries ► Molecular basis of Pol I and Pol III regulation
Keywords: Eukaryotic transcription; RNA polymerase I; RNA polymerase III; rRNAs; tRNAs; Structural biology
TFIIB-related factors in RNA polymerase I transcription by Bruce A. Knutson; Steven Hahn (pp. 265-273).
Eukaryotic RNA polymerases (Pol) I, II, III and archaeal Pol use a related set of general transcription factors to recognize promoter sequences and recruit Pol to promoters and to function at key points in the transcription initiation mechanism. The TFIIB-like general transcription factors (GTFs) function during several important and conserved steps in the initiation pathway for Pols II, III, and archaeal Pol. Until recently, the mechanism of Pol I initiation seemed unique, since it appeared to lack a GTF paralogous to the TFIIB-like proteins. The surprising recent discovery of TFIIB-related Pol I general factors in yeast and humans highlights the evolutionary conservation of transcription initiation mechanisms for all eukaryotic and archaeal Pols. These findings reveal new roles for the function of the Pol I GTFs and insight into the function of TFIIB-related factors. Models for Pol I transcription initiation are reexamined in light of these recent findings. This article is part of a Special Issue entitled: Transcription by Odd Pols.► A Pol I TFIIB-related factor has recently been discovered. ► Pol I TFIIB-related factors share many basic functions with TFIIB and Brf1. ► TAF1B and possibly Rrn7 function at a step post-polymerase recruitment. ► Eukaryotic Pol I, II, and III systems share a common evolutionary origin.
Keywords: Abbreviations; Pol; RNA polymerase; GTF; general transcription factor; rRNA; ribosomal RNA; rDNA; ribosomal DNA; CE; core element; TSS; transcription start site; UAS; upstream activating sequence; UCE; upstream control element; UAF; upstream activating factor; UBF; upstream binding factor; TBP; TATA binding protein; CF; core factor; SL1; selectivity factor 1; tWH; tandem winged helix; HMG; high mobility group protein; ChIP; chromatin immunoprecipitation; PIC; preinitiation complex; CTD; C-terminal domain; Brf; TFIIB-related factor; RPG; ribosomal protein genesRrn7; TAF1B; Pol I; TFIIB; Brf; rDNA transcription
Structure, function and regulation of Transcription Factor IIIA: From Xenopus to Arabidopsis by Elodie Layat; Aline V. Probst; Sylvette Tourmente (pp. 274-282).
Transcription Factor IIIA (TFIIIA) is specifically required for transcription of 5S ribosomal RNA, an essential component of the ribosome. The TFIIIA protein, found in every organism, has been characterized in several species. It shows remarkably poor conservation of primary protein sequence, but all orthologues analyzed carry several C2H2-zinc fingers that are required for TFIIIA binding to both 5S ribosomal DNA (rDNA) and RNA (rRNA). Alignments of TFIIIA protein and 5S rRNA gene sequences suggest a parallel evolution of the transcription factor and its natural binding site, the internal control region of the 5S rRNA gene. We discuss here how TFIIIA expression and availability in the cell is tightly regulated at the transcriptional, post-transcriptional and post-translational level to ensure adequate amounts of TFIIIA protein depending on cell type and developmental stage. This article is part of a Special Issue entitled: Transcription by Odd Pols.► TFIIIA functions as specific transcription factor for 5S rRNA genes ► TFIIIA zinc-fingers bind both 5S rDNA and the 5S rRNA gene product with high affinity. ► Sequence comparison suggests co-evolution of TFIIIA protein and 5S rRNA genes. ► TFIIIA availability is highly regulated to ensure cell-specific amounts of 5S rRNA.
Keywords: Abbreviations; 5S rRNA; 5S ribosomal RNA; 5S rRNA gene; 5S ribosomal RNA gene; 5S rDNA; 5S ribosomal DNA; TFIIIA; Transcription Factor IIIA; POl III; RNA Polymerase III; L5; Ribosomal Protein L5; zf; zinc finger; 5S RNP; 5S ribonucleoprotein particle composed of one L5 protein and one 5S rRNA molecule; 7S RNP; 7S ribonucleoprotein particle composed of one TFIIIA protein and one 5S rRNA molecule; 42S RNP; 42S ribonucleoprotein particle composed of one 5S rRNA molecule, one tRNA and two proteins, p43 and p48; Xl; TFIIIA; Xenopus laevis; TFIIIA; Sc; TFIIIA; Saccharomyces cerevisiae; TFIIIA; At; TFIIIA; Arabidopsis thaliana; TFIIIA; Sp; TFIIIA; Saccharomyces pombe; TFIIIATFIIIA; Zinc finger protein; 5S ribosomal RNA
Yeast RNA polymerase III transcription factors and effectors by Joël Acker; Christine Conesa; Olivier Lefebvre (pp. 283-295).
Recent data indicate that the well-defined transcription machinery of RNA polymerase III (Pol III) is probably more complex than commonly thought. In this review, we describe the yeast basal transcription factors of Pol III and their involvements in the transcription cycle. We also present a list of proteins detected on genes transcribed by Pol III (class III genes) that might participate in the transcription process. Surprisingly, several of these proteins are involved in RNA polymerase II transcription. Defining the role of these potential new effectors in Pol III transcription in vivo will be the challenge of the next few years. This article is part of a Special Issue entitled: Transcription by Odd Pols.► RNA polymerase III (Pol III) transcription in Saccharomyces cerevisiae is reviewed. ► We describe the discovery of the basal Pol III transcription machinery. ► We report recent advances in the knowledge of Pol III regulation. ► Components that may play a role in Pol III transcription in vivo are described.
Keywords: RNA polymerase III; Transcription; Saccharomyces cerevisiae; Chromatin immunoprecipitation
Identification of RNA polymerase III-transcribed genes in eukaryotic genomes by Giorgio Dieci; Anastasia Conti; Aldo Pagano; Davide Carnevali (pp. 296-305).
The RNA polymerase (Pol) III transcription system is devoted to the production of short, generally abundant noncoding (nc) RNAs in all eukaryotic cells. Previously thought to be restricted to a few housekeeping genes easily detectable in genome sequences, the set of known Pol III-transcribed genes (class III genes) has been expanding in the last ten years, and the issue of their detection, annotation and actual expression has been stimulated and revived by the results of recent high-resolution genome-wide location analyses of the mammalian Pol III machinery, together with those of Pol III-centered computational studies and of ncRNA-focused transcriptomic approaches. In this article, we provide an outline of distinctive features of Pol III-transcribed genes that have allowed and currently allow for their detection in genome sequences, we critically review the currently practiced strategies for the identification of novel class III genes and transcripts, and we discuss emerging themes in Pol III transcription regulation which might orient future transcriptomic studies. This article is part of a Special Issue entitled: Transcription by Odd Pols.► RNA polymerase III is specialized in the synthesis of short ncRNAs. ► Complete inventories of Pol III-transcribed ncRNA genes are still lacking. ► Genome-wide location analyses of Pol III machinery are helping to fill this gap. ► Defining Pol III transcriptomes also needs novel bioinformatic and RNomic strategies.
Keywords: RNA polymerase III; ncRNA; tRNA; SINE; TFIIIC; ChIP-seq
RNA polymerase I termination: Where is the end? by Nemeth Attila Németh; Jorge Perez-Fernandez; Philipp Merkl; Stephan Hamperl; Jochen Gerber; Joachim Griesenbeck; Herbert Tschochner (pp. 306-317).
The synthesis of ribosomal RNA (rRNA) precursor molecules by RNA polymerase I (Pol I) terminates with the dissociation of the protein–DNA–RNA ternary complex. Based on in vitro results the mechanism of Pol I termination appeared initially to be rather conserved and simple until this process was more thoroughly re-investigated in vivo. A picture emerged that Pol I termination seems to be connected to co-transcriptional processing, re-initiation of transcription and, possibly, other processes downstream of Pol I transcription units. In this article, our current understanding of the mechanism of Pol I termination and how this process might be implicated in other biological processes in yeast and mammals is summarized and discussed. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Characterisation of a new termination factor and its impact on the mechanism of termination. ► Factors required to dissociate the ternary transcription complex in mammals and yeast. ► Co-transcriptional pre-rRNA cleavage and termination. ► The possible role of termination for rDNA-loop formation and stimulation of transcription. ► The possible role of termination in rDNA stability and aging.
Keywords: Nucleolus; rRNA processing; rDNA chromatin; Aging; rDNA stability; Transcript release
Transcription termination by the eukaryotic RNA polymerase III by Aneeshkumar G. Arimbasseri; Keshab Rijal; Richard J. Maraia (pp. 318-330).
RNA polymerase (pol) III transcribes a multitude of tRNA and 5S rRNA genes as well as other small RNA genes distributed through the genome. By being sequence-specific, precise and efficient, transcription termination by pol III not only defines the 3′ end of the nascent RNA which directs subsequent association with the stabilizing La protein, it also prevents transcription into downstream DNA and promotes efficient recycling. Each of the RNA polymerases appears to have evolved unique mechanisms to initiate the process of termination in response to different types of termination signals. However, in eukaryotes much less is known about the final stage of termination, destabilization of the elongation complex with release of the RNA and DNA from the polymerase active center. By comparison to pols I and II, pol III exhibits the most direct coupling of the initial and final stages of termination, both of which occur at a short oligo(dT) tract on the non-template strand (dA on the template) of the DNA. While pol III termination is autonomous involving the core subunits C2 and probably C1, it also involves subunits C11, C37 and C53, which act on the pol III catalytic center and exhibit homology to the pol II elongation factor TFIIS and TFIIFα/β respectively. Here we compile knowledge of pol III termination and associate mutations that affect this process with structural elements of the polymerase that illustrate the importance of C53/37 both at its docking site on the pol III lobe and in the active center. The models suggest that some of these features may apply to the other eukaryotic pols. This article is part of a Special Issue entitled: Transcription by Odd Pols.► The rU:dA(5–6) hybrid is a destabilizing component during transcription termination. ► Pols I, II and III initiate termination differently but may share features thereafter. ► Several pol III subunits, including C2, C11, C53 and C37 contribute to termination. ► C37/53 and C11 are homologous to TFIIFα/β and TFIIS, respectively. ► Extraneous factors may be recruited to affect pol III termination in some cases.
Keywords: RPC11; RPC53; RPC37; RPC2; Intrinsic transcript cleavage; RNA:DNA hybrid
Transcription reinitiation by RNA polymerase III by Giorgio Dieci; Maria Cristina Bosio; Beatrice Fermi; Roberto Ferrari (pp. 331-341).
The retention of transcription proteins at an actively transcribed gene contributes to maintenance of the active transcriptional state and increases the rate of subsequent transcription cycles relative to the initial cycle. This process, called transcription reinitiation, generates the abundant RNAs in living cells. The persistence of stable preinitiation intermediates on activated genes representing at least a subset of basal transcription components has long been recognized as a shared feature of RNA polymerase (Pol) I, II and III-dependent transcription in eukaryotes. Studies of the Pol III transcription machinery and its target genes in eukaryotic genomes over the last fifteen years, has uncovered multiple details on transcription reinitiation. In addition to the basal transcription factors that recruit the polymerase, Pol III itself can be retained on the same gene through multiple transcription cycles by a facilitated recycling pathway. The molecular bases for facilitated recycling are progressively being revealed with advances in structural and functional studies. At the same time, progress in our understanding of Pol III transcriptional regulation in response to different environmental cues points to the specific mechanism of Pol III reinitiation as a key target of signaling pathway regulation of cell growth. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Facilitated recycling forces Pol III to reinitiate transcription on the same gene ► The macromolecular interactions underlying Pol III recycling are being unveiled. ► Fast Pol III reinitiation is essential for producing abundant Pol III transcripts. ► Facilitated Pol III recycling might be a key target in cell growth regulation.
Keywords: RNA polymerase III; TFIIIB; Gene looping; Sub1; Termination; Facilitated recycling
Dysregulation of RNA polymerase I transcription during disease by K.M. Hannan; E. Sanij; L.I. Rothblum; R.D. Hannan; R.B. Pearson (pp. 342-360).
Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme and subsequent processing of the ribosomal RNA are fundamental control steps in the synthesis of functional ribosomes.Dysregulation of Pol I transcription and ribosome biogenesis is linked to the etiology of a broad range of human diseases. Diseases caused by loss of function mutations in the molecular constituents of the ribosome, or factors intimately associated with RNA polymerase I transcription and processing are collectively termed ribosomopathies. Ribosomopathies are generally rare and treatment options are extremely limited tending to be more palliative than curative. Other more common diseases are associated with profound changes in cellular growth such as cardiac hypertrophy, atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I transcriptional activity in these diseases largely results from dysregulated upstream oncogenic pathways or by direct modulation by oncogenes or tumor suppressors at the level of the RNA polymerase I transcription apparatus itself. Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA processing or assembly factors have been covered by recent excellent reviews. In contrast, here we review our current knowledge of human diseases specifically associated with dysregulation of RNA polymerase I transcription and its associated regulatory apparatus, including some cases where this dysregulation is directly causative in disease. We will also provide insight into and discussion of possible therapeutic approaches to treat patients with dysregulated RNA polymerase I transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Dysregulation of RNA polymerase I transcription and ribosome biogenesis is linked to a broad range of human diseases. ► Ribosomopathies, hypertrophy, atrophy and cancer are all associated with dysregulation of RNA polymerase I transcription. ► Possible therapeutic approaches to treat patients with dysregulated RNA polymerase I transcription.
Keywords: RNA polymerase I transcription; Ribosomopathies; Cancer; Hypertrophy; Atrophy; Oncogene
Regulation of pol III transcription by nutrient and stress signaling pathways by Robyn D. Moir; Ian M. Willis (pp. 361-375).
Transcription by RNA polymerase III (pol III) is responsible for ~15% of total cellular transcription through the generation of small structured RNAs such as tRNA and 5S RNA. The coordinate synthesis of these molecules with ribosomal protein mRNAs and rRNA couples the production of ribosomes and their tRNA substrates and balances protein synthetic capacity with the growth requirements of the cell. Ribosome biogenesis in general and pol III transcription in particular is known to be regulated by nutrient availability, cell stress and cell cycle stage and is perturbed in pathological states. High throughput proteomic studies have catalogued modifications to pol III subunits, assembly, initiation and accessory factors but most of these modifications have yet to be linked to functional consequences. Here we review our current understanding of the major points of regulation in the pol III transcription apparatus, the targets of regulation and the signaling pathways known to regulate their function. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Pol III transcription is regulated by multiple conserved signaling pathways. ► The Maf1 repressor is phosphoregulated in response to nutrient and stress signals. ► TFIIIB and pol III are also differentially modified under stress conditions. ► Changes to TFIIIB and pol III function allow Maf1-dependent repression. ► Failsafe mechanisms prevent pol III repression in the absence of cell stress.
Keywords: Maf1; Rapamycin-sensitive TOR signaling; Cyclin-like kinase; Kns1; Glycogen synthase kinase; Protein kinase A; Protein kinase CK2
Maf1, a general negative regulator of RNA polymerase III in yeast by Magdalena Boguta (pp. 376-384).
tRNA synthesis by yeast RNA polymerase III (Pol III) is down-regulated under growth-limiting conditions. This control is mediated by Maf1, a global negative regulator of Pol III transcription. Conserved from yeast to man, Maf1 was originally discovered in Saccharomyces cerevisiae by a genetic approach. Details regarding the molecular basis of Pol III repression by Maf1 are now emerging from the recently reported structural and biochemical data on Pol III and Maf1. The phosphorylation status of Maf1 determines its nuclear localization and interaction with the Pol III complex and several Maf1 kinases have been identified to be involved in Pol III control. Moreover, Maf1 indirectly affects tRNA maturation and decay. Here I discuss the current understanding of the mechanisms that oversee the Maf1-mediated regulation of Pol III activity and the role of Maf1 in the control of tRNA biosynthesis in yeast. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Phenotypes of yeast maf1 mutants. ► Family of eukaryotic Maf1 proteins. ► Regulation of the activity of yeast Maf1. ► Model of Pol III regulation by Maf1 and CK2 kinase. ► Indirect effect of Maf1 on tRNA processing and decay.
Keywords: Transcription regulation; RNA polymerase III; tRNA synthesis; Maf1 repressor
RNA polymerase III repression by the retinoblastoma tumor suppressor protein by Alison Gjidoda; R. William Henry (pp. 385-392).
The retinoblastoma (RB) tumor suppressor protein regulates multiple pathways that influence cell growth, and as a key regulatory node, its function is inactivated in most cancer cells. In addition to its canonical roles in cell cycle control, RB functions as a global repressor of RNA polymerase (Pol) III transcription. Indeed, Pol III transcripts accumulate in cancer cells and their heightened levels are implicated in accelerated growth associated with RB dysfunction. Herein we review the mechanisms of RB repression for the different types of Pol III genes. For type 1 and type 2 genes, RB represses transcription through direct contacts with the core transcription machinery, notably Brf1–TFIIIB, and inhibits preinitiation complex formation and Pol III recruitment. A contrasting model for type 3 gene repression indicates that RB regulation involves stable and simultaneous promoter association by RB, the general transcription machinery including SNAPc, and Pol III, suggesting that RB may impede Pol III promoter escape or elongation. Interestingly, analysis of published genomic association data for RB and Pol III revealed added regulatory complexity for Pol III genes both during active growth and during arrested growth associated with quiescence and senescence. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Pol III transcripts accumulate in cancer cells. ► The retinoblastoma (RB) tumor suppressor represses global Pol III transcription. ► RB utilizes distinct repression mechanisms for different types of Pol III genes. ► Genomic analysis of RB and Pol III indicates dynamic regulation during growth arrest.
Keywords: RNA polymerase III; Retinoblastoma; Transcription; Repression; Chromatin; Cell cycle
Epigenetic control of RNA polymerase I transcription in mammalian cells by Ingrid Grummt; Langst Gernot Längst (pp. 393-404).
rRNA synthesis is regulated by genetic and epigenetic mechanisms. Epigenetic states are metastable, changing in response to appropriate signals, thereby modulating transcription in vivo. The establishment, maintenance and reversal of epigenetic features are fundamental for the cell's ability to ‘remember’ past events, to adapt to environmental changes or developmental cues and to propagate this information to the progeny. As packaging into chromatin is critical for the stability and integrity of repetitive DNA, keeping a fraction of rRNA genes in a metastable heterochromatic conformation prevents aberrant exchanges between repeats, thus safeguarding nucleolar structure and rDNA stability. In this review, we will focus on the nature of the molecular signatures that characterize a given epigenetic state of rDNA in mammalian cells, including noncoding RNA, DNA methylation and histone modifications, and the mechanisms by which they are established and maintained. This article is part of a Special Issue entitled: Transcription by Odd Pols.► Reviews structural features of active, silent and poised rRNA genes. ► Describes the pathways that establish distinct epigenetic states of rRNA genes. ► Highlights the role of noncoding RNA in epigenetic regulation. ► Discusses the impact of external signals on epigenetic regulation of rRNA synthesis.
Keywords: RNA polymerase I; Epigenetics; Nucleosome positioning; Histone modifications; DNA methylation; Noncoding RNA
Chromatin states at ribosomal DNA loci by Stephan Hamperl; Manuel Wittner; Virginia Babl; Jorge Perez-Fernandez; Herbert Tschochner; Joachim Griesenbeck (pp. 405-417).
Eukaryotic transcription of ribosomal RNAs (rRNAs) by RNA polymerase I can account for more than half of the total cellular transcripts depending on organism and growth condition. To support this level of expression, eukaryotic rRNA genes are present in multiple copies. Interestingly, these genes co-exist in different chromatin states that may differ significantly in their nucleosome content and generally correlate well with transcriptional activity. Here we review how these chromatin states have been discovered and characterized focusing particularly on their structural protein components. The establishment and maintenance of rRNA gene chromatin states and their impact on rRNA synthesis are discussed. This article is part of a Special Issue entitled: Transcription by Odd Pols.► The ribosomal RNA (rRNA) genes transcribed by RNA polymerase I coexist in different chromatin states. ► Many structural and molecular features of the chromatin states are conserved in eukaryotes. ► The rRNA gene chromatin states are dynamic and respond to essential cellular processes. ► The maintenance of rRNA gene chromatin states is important to guarantee ribosome production and genome stability.
Keywords: Abbreviations; ChEC/ChIC; chromatin endogenous/immuno cleavage; ChIP; chromatin immunoprecipitation; EM; electron microscopy; HMG; high mobility group; IGS; intergenic spacer; NER; nucleotide excision repair; NOR; nucleolar organizer region; PIC; preinitiation complex; Pol I; RNA polymerase I; rDNA; ribosomal DNA; rRNA; ribosomal RNA; UAF; upstream activation factor; UBF; upstream binding factorChromatin; Transcription; Ribosomal RNA genes; Ribosomal DNA;HMG-box protein; RNA polymerase I; Nucleosome
TFIIIC bound DNA elements in nuclear organization and insulation by Jacob G. Kirkland; Jesse R. Raab; Rohinton T. Kamakaka (pp. 418-424).
tRNA genes (tDNAs) have been known to have barrier insulator function in budding yeast, Saccharomyces cerevisiae, for over a decade. tDNAs also play a role in genome organization by clustering at sites in the nucleus and both of these functions are dependent on the transcription factor TFIIIC. More recently TFIIIC bound sites devoid of pol III, termed Extra-TFIIIC sites (ETC) have been identified in budding yeast and these sites also function as insulators and affect genome organization. Subsequent studies in Schizosaccharomyces pombe showed that TFIIIC bound sites were insulators and also functioned as Chromosome Organization Clamps (COC); tethering the sites to the nuclear periphery. Very recently studies have moved to mammalian systems where pol III genes and their associated factors have been investigated in both mouse and human cells. Short interspersed nuclear elements (SINEs) that bind TFIIIC, function as insulator elements and tDNAs can also function as both enhancer — blocking and barrier insulators in these organisms. It was also recently shown that tDNAs cluster with other tDNAs and with ETCs but not with pol II transcribed genes. Intriguingly, TFIIIC is often found near pol II transcription start sites and it remains unclear what the consequences of TFIIIC based genomic organization are and what influence pol III factors have on pol II transcribed genes and vice versa. In this review we provide a comprehensive overview of the known data on pol III factors in insulation and genome organization and identify the many open questions that require further investigation. This article is part of a Special Issue entitled: Transcription by Odd Pols.► TFIIIC is a key transcription factor in tRNA gene transcription. ► Some TFIIIC bound sites, function as gene insulators across species. ► Chromatin remodeling/modifying cofactors contribute to TFIIIC mediated insulation. ► TFIIIC also coordinates higher order chromatin folding in the nucleus.
Keywords: TFIIIC; Insulator; tDNA; Chromatin folding