Transcription

  • Article
    | Open Access

    Transcription in archaea is known to be regulated through the recruitment of RNA polymerase to promoters. Here, the authors show that the archaeon Saccharolobus solfataricus regulates transcription globally through a rate-limiting promoter-proximal elongation step.

    • Fabian Blombach
    • , Thomas Fouqueau
    •  & Finn Werner
  • Article
    | Open Access

    Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

    • Hiroki Sugishita
    • , Takashi Kondo
    •  & Haruhiko Koseki
  • Article
    | Open Access

    Cells in the developing embryo interpret WNT signalling with context-dependence, but the mechanism decoding these cues is unclear. Here, the authors show that combinatorial TALE/HOX activity destabilizes nucleosomes at WNT-responsive regions to activate paraxial mesodermal genes.

    • Luca Mariani
    • , Xiaogang Guo
    •  & Elisabetta Ferretti
  • Article
    | Open Access

    The chromatin remodeler Chd1 mediates hypertranscription in embryonic stem (ES) cells and has been shown to associate with genes transcribed by RNA Polymerase (Pol) I and II. Here the authors provide mechanistic insights into this process and reveal that Chd1 is involved in protecting genome integrity at promoter regions by preventing DNA break accumulation.

    • Aydan Bulut-Karslioglu
    • , Hu Jin
    •  & Miguel Ramalho-Santos
  • Article
    | Open Access

    Here the authors decode how core promoter elements regulate rate limiting steps of transcription using quantitative live imaging, genetics and modeling in early Drosophila embryos. TATA-driven promoters require one rate-limiting step while INR promoters need an extra step associated with Pol II pausing.

    • Virginia L. Pimmett
    • , Matthieu Dejean
    •  & Mounia Lagha
  • Article
    | Open Access

    The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

    • Katjana Tantale
    • , Encar Garcia-Oliver
    •  & Edouard Bertrand
  • Article
    | Open Access

    Kras is frequently mutated in lung cancer and two isoforms are generated via alternative splicing. Here, the authors show that the two isoforms have divergent roles in cancer stem cells and the main tumour cell population, which are regulated by hypoxia and endoplasmic reticulum stress.

    • Wei-Ching Chen
    • , Minh D. To
    •  & Allan Balmain
  • Article
    | Open Access

    Accurate regulation of protein concentrations according to changes in cell volume that accompany growth and changes in biosynthetic capacity is an important component of cellular homeostasis. Here, using the model organism S. cerevisiae, the authors show how histone production is quantitatively coupled to genome content through the intrinsic properties of histone promoters.

    • Kora-Lee Claude
    • , Daniela Bureik
    •  & Kurt M. Schmoller
  • Article
    | Open Access

    Mutations in 5’ untranslated regions (UTRs) have a functional role in gene expression in cancer. Here, the authors develop a sequencing-based high throughput functional assay named PLUMAGE and show the effects of these mutations on gene expression and their association with clinical outcomes in prostate cancer.

    • Yiting Lim
    • , Sonali Arora
    •  & Andrew C. Hsieh
  • Article
    | Open Access

    STAT1a is required for pro-inflammatory responses in macrophages. Here the authors reveal that post-translational modification of STAT1a, ADPribosylation, plays a critical role in enhancer formation and activation, thus modulating IFNγ-stimulated inflammatory responses in macrophages.

    • Rebecca Gupte
    • , Tulip Nandu
    •  & W. Lee Kraus
  • Article
    | Open Access

    How gene expression reactivation is promoted following DNA damage is not yet clear. Here, the authors identify a role for the human histone chaperone complex HIRA in transcription restart following UV damage independently of its function in new H3.3 histone deposition.

    • Déborah Bouvier
    • , Juliette Ferrand
    •  & Sophie E. Polo
  • Article
    | Open Access

    Transcription factors (TFs) often form distinct networks to regulate transcriptional program during cancer progression. Here the authors show that OCT4 is a common transcriptional factor in two types of advanced PC and as such, OCT4 accelerates a TF complex formation with the FOXA1/AR in castration-resistant PC and NRF1 in neuroendocrine PC.

    • Ken-ichi Takayama
    • , Takeo Kosaka
    •  & Satoshi Inoue
  • Article
    | Open Access

    A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

    • Long Jin
    • , Qianzi Tang
    •  & Mingzhou Li
  • Article
    | Open Access

    Phc1 is a subunit of the polycomb repressive complex 1 (PRC1), which represses gene expression during development. Here the authors show that Phc1 acts independently from PRC1 to activate Nanog transcription by stabilizing genome-wide chromatin interactions of the Nanog locus, and in turn stabilize pluripotency.

    • Li Chen
    • , Qiaoqiao Tong
    •  & Junfeng Ji
  • Article
    | Open Access

    Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Here the authors present a meta-analysis empowered by a new statistical method covering thousands of ChIP-Seq experiments resulting in the identification of more than 500 thousand allele-specific binding (ASB) events in the human genome.

    • Sergey Abramov
    • , Alexandr Boytsov
    •  & Ivan V. Kulakovskiy
  • Article
    | Open Access

    The MerR family of transcriptional regulators, such as EcmrR, activate promoters with a structure that is suboptimal for recognition by RNA polymerase holoenzyme. Structural insights into the EcmrR-dependent transcription process elucidate the mechanisms enabling optimal promoter recognition and transition from initiation to elongation.

    • Yang Yang
    • , Chang Liu
    •  & Bin Liu
  • Article
    | Open Access

    Histone variant H2A.Z has been suggested to contribute to the regulation of promoter accessibility. Here, the authors present high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for human Pol II promoters and provide evidence that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter.

    • Lauren Cole
    • , Sebastian Kurscheid
    •  & David J. Tremethick
  • Article
    | Open Access

    Whether chronic inflammation contributes to metabolic disease through the dysregulation of circadian systems remains incompletely understood in humans. Here the authors show that circadian clock function is perturbed in adipose tissue from individuals with obesity, and that inhibition of NFkB improves clock function.

    • Eleonore Maury
    • , Benoit Navez
    •  & Sonia M. Brichard
  • Article
    | Open Access

    Acheiropodia is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development, but how these deletions lead to this phenotype is unknown. Here the authors use whole-genome sequencing, ChIP-seq, 4C-seq and DNA FISH to show that alterations in CTCF motifs are responsible via altered enhancer–promoter interactions.

    • Aki Ushiki
    • , Yichi Zhang
    •  & Nadav Ahituv
  • Article
    | Open Access

    The intrinsically disordered acidic activation domain (AD) of the yeast transcription factor Gal4 acts through binding to the Med15 subunit of the Mediator complex. Here, the authors show that Gal4 interacts with Med15 through an identical fuzzy binding mechanism as Gcn4 AD, which has a different sequence, revealing a common sequence-independent mechanism for AD-Mediator binding. In contrast, Gal4 AD binds to the Gal80 repressor as a structured polypeptide, which strongly suggests that the structured binding partner dictates the type of protein–protein interaction for an intrinsically disordered protein.

    • Lisa M. Tuttle
    • , Derek Pacheco
    •  & Rachel E. Klevit
  • Article
    | Open Access

    The role of transcriptional enhancers and 3D chromatin organisation in coordinating the transition from naive to primed pluripotency remains poorly understood. Here the authors generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells to provide insights into these developmental processes.

    • Peter Chovanec
    • , Amanda J. Collier
    •  & Peter J. Rugg-Gunn
  • Article
    | Open Access

    Glucocorticoid receptors (GR) are thought to bind DNA as dimers or monomers, to regulate different transcription pathways. Here, the authors perform genome-wide studies on GRs with mutations that impair dimerization and provide evidence that monomeric GRs do not play a significant physiologic role.

    • Thomas A. Johnson
    • , Ville Paakinaho
    •  & Diego M. Presman
  • Article
    | Open Access

    The GntR superfamily is one of the largest families of transcription factors in prokaryotes. Here the authors combine biophysical analysis and structural biology to dissect the mechanism by which NanR — a GntR-family regulator — binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.

    • Christopher R. Horne
    • , Hariprasad Venugopal
    •  & Renwick C. J. Dobson
  • Article
    | Open Access

    Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations. Here the authors develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection.

    • Yun Heacock-Kang
    • , Ian A. McMillan
    •  & Tung T. Hoang
  • Article
    | Open Access

    Biogenesis of small nucleolar RNAs ribonucleoproteins (snoRNPs) requires dedicated assembly machinery. Here, the authors show that a subset of snoRNP assembly factors interacts, genetically or directly, with factors modulating chromatin architecture, suggesting a link between ribosome formation and chromatin functions.

    • Benoît Bragantini
    • , Christophe Charron
    •  & Bruno Charpentier
  • Article
    | Open Access

    In Pseudomonas aeruginosa, the protein AlpA activates the expression of the alp locus in response to DNA damage, leading to lysis in a subset of cells and enhancing virulence of other, surviving cells. Here, the authors show that AlpA acts as an antiterminator rather than a transcriptional activator.

    • Jennifer M. Peña
    • , Samantha M. Prezioso
    •  & Simon L. Dove
  • Article
    | Open Access

    While recent studies suggest that transcriptional activators form condensates at active loci, less is known about the distribution of repressor proteins. Here, the authors develop an expression assay in living Ciona embryos and visualize puncta of Hes repressors, with the Groucho/TLE corepressor, observing that the Hes.a/Gro puncta have the properties of viscous liquid droplets that undergo limited fusion events due to association with DNA.

    • Nicholas Treen
    • , Shunsuke F. Shimobayashi
    •  & Michael Levine
  • Article
    | Open Access

    DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO.

    • Karina Mendes
    • , Sandra Schmidhofer
    •  & Michael Rehli
  • Article
    | Open Access

    A quantitative assessment of promoter function can improve the precision of cellular engineering. Here the authors develop a method to simultaneously count plasmid DNA, RNA transcripts and protein expression in single living bacteria.

    • Bin Shao
    • , Jayan Rammohan
    •  & Christopher A. Voigt
  • Article
    | Open Access

    The methylation of Histone 3 at Lysine 36 (H3K36) has been implicated in the regulation of transcription and coupled processes such as mRNA splicing. Here the authors show that the histone methyltransferase SETD2 interacts with hnRNP L to mediate the crosstalk between the transcription and splicing machineries.

    • Saikat Bhattacharya
    • , Michaella J. Levy
    •  & Jerry L. Workman
  • Article
    | Open Access

    The response to hypoxia can significantly impact oncogenic processes. Here, the authors define the early transcriptional response to acute hypoxia and identify HIF1A target genes as part of this acute response, providing a resource for investigating context-dependent roles of HIF1A in the biology of cancer.

    • Zdenek Andrysik
    • , Heather Bender
    •  & Joaquin M. Espinosa
  • Article
    | Open Access

    Interaction between transcription factors and chromatin is fundamental for genome organization and regulation. Here, the authors use information theory to measure signatures of organized chromatin resulting from transcription factor-chromatin interactions, termed chromatin information enrichment, and find that variations in the information encoded in chromatin architecture reflects functional biological variation.

    • Ricardo D’Oliveira Albanus
    • , Yasuhiro Kyono
    •  & Stephen C. J. Parker
  • Article
    | Open Access

    The transcription-coupled repair pathway removes transcription-blocking DNA lesions, but how transcription is restored following DNA repair is not clear. Here the authors reveal that the PAF1 complex, while dispensable for the repair process, restores transcription after DNA damage.

    • Diana van den Heuvel
    • , Cornelia G. Spruijt
    •  & Martijn S. Luijsterburg
  • Article
    | Open Access

    The noncoding RNA 7SK controls the transcription of mRNAs. Here, the authors show that the 7SK complex interacts with the Smn complex, suggesting crosstalk between transcription and snRNP assembly.

    • Changhe Ji
    • , Jakob Bader
    •  & Michael Briese
  • Article
    | Open Access

    Transcription activation of late genes in T4 bacteriophage requires the promoter specificity factor gp55, the coactivator gp33 and the sliding clamp gp45. Here, the authors provide structural insights into gp45- dependent transcription activation by determining the cryo-EM structures of a gp55-dependent RNA polymerase (RNAP)-promoter open complex and of an intact gp45-dependent transcription activation complex.

    • Jing Shi
    • , Aijia Wen
    •  & Yu Feng
  • Article
    | Open Access

    Although the Drosophila genome has widespread contact domains and CTCF, it remains unclear whether CTCF-dependent domains exist in flies. Here, the authors ablate CTCF in Drosophila and find that CTCF is required to form a small fraction of all domain boundaries, suggesting differences in the role of CTCF for genome folding in flies and vertebrates.

    • Anjali Kaushal
    • , Giriram Mohana
    •  & Maria Cristina Gambetta
  • Article
    | Open Access

    Transcription by bacterial RNA polymerase is interrupted by pausing events that play diverse regulatory roles. Here, the authors find that a large number of E. coli sigma70-dependent pauses, clustered at a 10−20-bp distance from promoters, are regulated by Gre cleavage factors constituting a mechanism for rapid response to changing environmental cues.

    • Zhe Sun
    • , Alexander V. Yakhnin
    •  & Mikhail Kashlev
  • Article
    | Open Access

    RNA and DNA polymerases need to discriminate efficiently against closely related nucleotide triphosphate substrates. Here, the authors show that a conserved Arg residue is the major determinant of selectivity against deoxyribonucleoside substrates by multisubunit RNA polymerases.

    • Janne J. Mäkinen
    • , Yeonoh Shin
    •  & Georgiy A. Belogurov
  • Article
    | Open Access

    The role of RNA polymerase II (Pol II) recruitment during adult stem cell differentiation is well understood, but not that of Pol II elongation. Here, the authors show that 30% of epidermal stem cell differentiation genes depend on SPT6 and PAF1 for Pol II elongation, and SPT6 loss leads to an intestine-like phenotype.

    • Jingting Li
    • , Xiaojun Xu
    •  & George L. Sen
  • Article
    | Open Access

    RNA polymerase (Pol) I transcribes the ribosomal RNA precursor in eukaryotes. Here, the authors present three cryo-EM structure of S. pombe Pol I in different functional states among them a dimer structure and discuss conserved and organism-specific features of Pol I.

    • Florian B. Heiss
    • , Julia L. Daiß
    •  & Christoph Engel
  • Article
    | Open Access

    Ribosomal RNA (rRNA) expression is regulated at the initiation stage of RNA synthesis. Here, the authors report cryo-EM structures of E. coli RNA polymerase and rRNA promoter complex with DksA/ppGpp on the way to open complex formation, identifying key steps in promoter recognition and opening.

    • Yeonoh Shin
    • , M. Zuhaib Qayyum
    •  & Katsuhiko S. Murakami