Studying Enhancer Elements with Lambda
Bacteriophage lambda has been crucial in revealing fundamental principles underlying the control of transcription by elements positioned close to promoters. In this issue, Cui et al. discusses how lambda also provides a model for long-range gene regulation, including the action of enhancer elements.
Controlling the Clock
Circadian clocks tune the physiology of organisms to periodic changes in the environment in a dynamic fashion. Clock-controlled biological processes have been extensively studied in various model species and encompass cytosolic, genetic and metabolic dimensions. In multicellular organisms, the clock network is organized in a tissue-specific manner. Schippers et al. now discuss how these different dimensions communicate with each other and how tissue-specific clocks exchange temporal information within multicellular organisms.
Transcript Assisted Hydrolysis by Eukaryotic RNAP II
Hydrolysis of the phosphodiester bonds of the transcript by bacterial RNA polymerase is assisted by a nucleotide monophosphate at the 3′ end of the RNA. Now, Nielsen and Zenkin provide evidence that this mechanism is also involved in RNA cleavage by eukaryotic RNA polymerase II, suggesting that transcript assisted hydrolysis has emerged before divergence of bacteria and archaea/eukaryotes.
Regulation of Context-Specific Gene Expression
Specific combinations of RNA-binding–proteins (RBPs) and microRNAs conjointly contribute to the complexity of posttranscriptional control of mRNAs. Sundaram and Sampath now discuss how posttranscriptional switches regulated by RBPs control context-specific expression of two alternative gene products from a single transcript.
The Zinc in RNA Polymerase I
Most RNA polymerases contain zinc. A recent study provides evidence that zinc levels control the stability of RNA polymerase I in vivo and that the enzyme might serve as a zinc reservoir for other proteins. In this issue, Chanfreau discusses the implications of this discovery.
Stimulatory and Repressive Functions of Histone H2B Ubiquitin Ligase
Histone H2B ubiquitylation is involved in transcription regulation and other DNA transacting processes. In this issue, Sen and Bhaumik discuss recent studies that have implicated both transcriptional stimulatory and repressive functions of histone H2B ubiquitin ligase at the same or different genes.
STAT3 as a Regulator of Chromatin Topology
Recently, a role for transcription factors in reorganization of the three-dimensional genome structure has been suggested. Distribution of signal transducer and activator of transcription (STAT) binding sites on genomic DNA and the ability of this family of transcription factors to form phosphorylated (P-STAT) tetramers and unphosphorylated (U-STAT) dimers suggest that some family members, particularly STAT3, may be directly involved in regulation of chromatin topology. Zhao et al. discuss here the potential roles for STAT3 and other STAT family members in the regulation of gene expression by modulation of chromatin organization.
Beyond the Standard Role of DNA Topoisomerases
Changes in chromatin structure are linked to changes of DNA topology, which might itself serve as a regulatory signal to be detected by proteins. In that way, DNA Topoisomerases may contribute to the regulation of many events occurring during the transcription cycle. Baranello et al. review the functions of DNA Topoisomerases in transcription, focusing on the roles beyond their task of solving topological problems associated with transcription elongation.
Topoisomerase II in Dosage Compensation
In Drosophila, dosage compensation is mediated by the MSL complex, which binds numerous sites on the X chromosome in males and enhances the transcriptional rate of numerous X-linked genes. Topoisomerase II (Topo II) is enriched on dosage compensated genes, to which it is recruited by association with the MSL complex, in excess of the amount that is present on autosomal genes with similar transcription levels. In this issue, Cugusi et al. elegantly show that Topo II is required for proper dosage compensation and that compensated chromatin is topologically different from non-compensated chromatin. This difference requires the function of Topo II. This work suggests that Topo II is an integral part of the mechanistic basis of dosage compensation.
Unique Role of SRSF2 in Transcription Activation
Transcription pause release from gene promoters is a critical point for transcriptional regulation in higher eukaryotes. Recently, regulatory RNAs have been shown to be involved in transcriptional control, together with various RNA binding proteins. SRSF2, a member of the SR family of splicing regulators, was shown to play a role in binding to promoter-associated small RNA to mediate transcription pause release. Now, Mo et al. further dissect the structural requirement for SRSF2 to function as a transcription activator and extend the analysis to multiple SR and hnRNP proteins by using the MS2 tethering strategy. Their findings suggest broad participation of RNA binding proteins in diverse aspects of regulated gene expression at both the transcriptional and posttranscriptional levels in mammalian cells.
HoxB Gene Expression and Actin Polymerization
The eukaryotic nucleus is compartmentalized in chromatin domains, which can be permissive or restrictive of transcription. This process occurs in specific nuclear subregions in which active genes are concentrated together with RNA polymerase II and DNA- and RNA-binding factors. In this issue, Naum-Onganía et al. studied the regulation of the HoxB cluster, which is activated by retinoic acid and transcribed in a collinear manner. The DNA-binding Pknox1-Pbx1 complex modulates Hox protein activity. The authors have now used NT2-D1 teratocarcinoma cells, a model of Hox gene expression, to show that, upon retinoic acid induction, Pknox1 co-localizes with polymeric nuclear actin. They show that that globular actin aggregates, polymeric actin, the elongating RNA polymerase II, and THOC match euchromatic regions corresponding to nuclear speckles, supporting the hypothesis that nuclear actin polymerization is involved in the activation of HoxB gene expression by means of nuclear speckles.
Meeting Report
This issue includes an excellent report on the “Mechanisms of Eukaryotic Transcription” meeting held at Cold Spring Harbor Laboratory, Cold Spring Harbor, NY in August 2013.