Transcriptional regulatory elements articles within Nature Communications

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  • Article
    | Open Access

    The role of BRD4 and Mediator in regulating enhancer-promoter interactions is poorly understood. Here the authors find that treatment with BET inhibitors or pharmacological degradation of BRD4 disrupts transcription while having very little effect on enhancer-promoter interactions.

    • Nicholas T. Crump
    • , Erica Ballabio
    •  & Thomas A. Milne

  • Article
    | Open Access

    Genomes are partitioned into topologically associating domains (TADs). Here the authors present single-nucleus Hi-C maps in Drosophila at 10 kb resolution, demonstrating the presence of chromatin compartments in individual nuclei, and partitioning of the genome into non-hierarchical TADs at the scale of 100 kb, which resembles population TAD profiles.

    • Sergey V. Ulianov
    • , Vlada V. Zakharova
    •  & Sergey V. Razin

  • Article
    | Open Access

    Hepatocyte 12-hour rhythms have a role in cellular stress and metabolic functions. Here, the authors demonstrate disrupting the 12-hour clock through deletion of XBP1 is associated with the development of NAFLD as well as disruption of phospholipid composition and the maintenance of lipid homeostasis.

    • Huan Meng
    • , Naomi M. Gonzales
    •  & Bert W. O’Malley

  • Article
    | Open Access

    Histone 3 Lys 27 trimethylation (H3K27me3) mediates epigenetic silencing of gene expression. Here, Zhang et al. show that in Arabidopsis, the BAH-domain H3K27me3-reader protein AIPP3 forms a complex with PHD proteins and CPL2, a plant-specific Pol II phosphatase, to inhibit Pol II activity by dephosphorylation.

    • Yi-Zhe Zhang
    • , Jianlong Yuan
    •  & Cheng-Guo Duan

  • Article
    | Open Access

    The TGFβ signaling pathway has been shown to regulate transcription by regulating enhancer activity. Here, the authors perform a comprehensive analysis of enhancers in normal mammary epithelial gland cells to elucidate how TGFβ-dependent enhancers control gene transcription in these cells.

    • Jose A. Guerrero-Martínez
    • , María Ceballos-Chávez
    •  & Jose C. Reyes

  • Article
    | Open Access

    Enhancer RNAs are transcribed bidirectionally from core transcription initiation regions. Here, by employing nascent RNA sequencing, the authors identify quantitative trait loci (QTLs) associated with enhancer RNA level and directionality, revealing the bipartite architecture of enhancers.

    • Katla Kristjánsdóttir
    • , Alexis Dziubek
    •  & Hojoong Kwak

  • Article
    | Open Access

    The ATF2 transcription factor is phosphorylated by different mitogen-activated protein (MAP) kinases. Here, the authors show that the functionally distinct MAP kinases JNK and p38 control ATF2 through different binding sites and differential phosphorylation, thereby modulating ATF2’s sensitivity to the JNK and p38 pathways.

    • Klára Kirsch
    • , András Zeke
    •  & Attila Reményi

  • Article
    | Open Access

    The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide.

    • Christopher H. Douse
    • , Iva A. Tchasovnikarova
    •  & Yorgo Modis

  • Article
    | Open Access

    Transcription factor TFIIIC plays roles in Pol III transcription and in chromatin organization. CryoEM structure of the yeast TFIIIC subcomplex τA, a negative stain reconstruction of τA bound to the TFIIIB subunits Brf1 and TBP and accompanying biochemistry suggest how τA achieves positioning of TFIIIB upstream of the TSS and remodeling of the TFIIIC complex during assembly of TFIIIB.

    • Matthias K. Vorländer
    • , Anna Jungblut
    •  & Christoph W. Müller

  • Article
    | Open Access

    Super-enhancer are usually defined by high levels of chromatin modification and associate with cell-specific gene expression. Here, the authors define hyperacetylated chromatin domains (HCDs) by using histone hyperacetylation peak breadth information and show that HCDs associated more closely with cell identity than super-enhancers.

    • Sierra Fox
    • , Jacquelyn A. Myers
    •  & Michael Bulger

  • Article
    | Open Access

    S. cerevisiae TBP associated factor 14 (Taf14) is a transcriptional regulator that interacts with multiple nuclear complexes. Here, the authors report that the extra-terminal domain of Taf14 (Taf14ET) recognizes a common motif in various transcriptional coactivator proteins and they solve the NMR structure of Taf14ET bound the ET-binding motif of Sth1, the catalytic subunit of the RSC (Remodel the Structure of Chromatin) complex, and furthermore show that Taf14ET undergoes liquid-liquid phase separation, which is enhanced by Taf14 interaction partners.

    • Guochao Chen
    • , Duo Wang
    •  & Yong Chen

  • Article
    | Open Access

    GATA 3 functions as a pioneer factor during cellular reprogramming. Here the authors delineate nucleosome positioning relative to GATA3 binding motifs and describe the structure of a GATA3–nucleosome complex; providing insight into how a pioneer factor interacts with nucleosomes and catalyze their local remodelling to produce an accessible enhancer.

    • Hiroki Tanaka
    • , Yoshimasa Takizawa
    •  & Hitoshi Kurumizaka

  • Article
    | Open Access

    Transposable elements are a potential source of transcriptional regulators, but how these sequences contribute to oncogenesis remains poorly understood. Here, the authors identify endogenous retroviruses (ERVs) with acute myeloid leukemia (AML)-associated enhancer chromatin signatures, and provide evidence that ERV activation provides an additional layer of gene regulation in AML.

    • Özgen Deniz
    • , Mamataz Ahmed
    •  & Miguel R. Branco

  • Article
    | Open Access

    Acute kidney injury is a major health problem amongst hospitalized patients. Here the authors provide a comprehensive characterization of enhancer and super-enhancer elements, and the transcription factor motifs associated with these elements in response to kidney injury in vivo; providing insight into the regulation of kidney repair.

    • Julia Wilflingseder
    • , Michaela Willi
    •  & Joseph V. Bonventre

  • Article
    | Open Access

    In budding yeast, the decision to enter meiosis is defined by nutrient and mating-type signals regulating expression of the master transcription factor for meiotic entry, IME1. Here, the authors characterize the steps involved in regulating the entering in meiosis via the co-repressor complex Tup1-Cyc8.

    • Janis Tam
    •  & Folkert J. van Werven

  • Article
    | Open Access

    Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

    • Katrin Fischer
    • , Anna Fenzl
    •  & Timo D. Müller

  • Article
    | Open Access

    Identification of silencer elements by computational or experimental approaches in a genome-wide manner is still challenging. Here authors define uncharacterized cis-regulatory elements (CREs) in human and mouse genomes likely containing silencer elements, and test them in cells using massively parallel reporter assays to identify silencer elements that showed silencer activity.

    • Naresh Doni Jayavelu
    • , Ajay Jajodia
    •  & R. David Hawkins

  • Article
    | Open Access

    Nucleosome organisation plays important roles in regulating functional genomic elements. Here, the authors use high-resolution profiling to analyse dynamic nucleosome positioning at inducible and cell-type-specific promoters, providing a global view of chromatin architecture at inducible promoters.

    • Agata Oruba
    • , Simona Saccani
    •  & Dominic van Essen

  • Article
    | Open Access

    Engineering mammalian cellular functions requires a toolkit of orthogonal and well-characterized genetic components. Here the authors develop COMET: an ensemble of transcription factors, promoters, and accompanying models for the design and construction of genetic programs.

    • Patrick S. Donahue
    • , Joseph W. Draut
    •  & Joshua N. Leonard

  • Article
    | Open Access

    The functional significance of start site choice in promoter architectures is little understood. Here the authors identify in zebrafish development and mammalian cells a class of dual-initiation promoters, in which non-canonical YC dinucleotides reflecting 5’-TOP/TCT initiation are intertwined with canonical YR-initiation.

    • Chirag Nepal
    • , Yavor Hadzhiev
    •  & Ferenc Müller

  • Article
    | Open Access

    Although transcription factor (TF) cooperativity is widespread, a global mechanistic understanding of the role of TF cooperativity is still lacking. Here the authors introduce a statistical learning framework that provides structural insight into TF cooperativity and its functional consequences based on next generation sequencing data and provide mechanistic insights into TF cooperativity and its impact on protein-phenotype interactions.

    • Ignacio L. Ibarra
    • , Nele M. Hollmann
    •  & Judith B. Zaugg

  • Article
    | Open Access

    The BEN-solo proteins—including Insensitive (Insv), Elba1 and Elba2—function in both transcriptional repression and chromatin insulation. Here, the authors investigate the role of these proteins in Drosophila embryos, finding that ELBA and Insv function as general insulators and partition active chromatin to ensure proper gene activation in Drosophila.

    • Malin Ueberschär
    • , Huazhen Wang
    •  & Qi Dai

  • Article
    | Open Access

    RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.

    • Yashar Sadian
    • , Florence Baudin
    •  & Christoph W. Müller

  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    •  & Jim R. Hughes

  • Article
    | Open Access

    Mutations associated with SCN5A, which encodes the major cardiac sodium channel, influence impulse conduction and are associated with arrhythmia disorders. Here, the authors identify an evolutionary conserved, super enhancer-like, regulatory cluster downstream of SCN5A and show that it controls the chromatin architecture of the locus and Scn5a expression.

    • Joyce C. K. Man
    • , Rajiv A. Mohan
    •  & Vincent M. Christoffels

  • Article
    | Open Access

    The majority of disease-associated genetic variants lie in non-coding regions. Here the authors generated and compiled human transcriptomic, epigenomic and chromatin conformation datasets, to identify genes associated with atrial fibrillation and functional non-coding variants.

    • Antoinette F. van Ouwerkerk
    • , Fernanda M. Bosada
    •  & Vincent M. Christoffels

  • Article
    | Open Access

    Numerous tissues are derived from the lateral plate mesoderm (LPM) but how this is specified is unclear. Here, the authors identify a pan-LPM reporter activity found in the zebrafish draculin (drl) gene that also shows transgenic activity in LPM-corresponding territories of several chordates, including chicken, axolotl, lamprey, Ciona, and amphioxus.

    • Karin D. Prummel
    • , Christopher Hess
    •  & Christian Mosimann

  • Article
    | Open Access

    Hox proteins are expressed in partially overlapping regions to inform development along the embryo’s head-tail axis. Here the authors analyse a cis regulatory module directly regulated by seven different Drosophila Hox proteins to uncover how different Hox class proteins differentially control its expression.

    • Carlos Sánchez-Higueras
    • , Chaitanya Rastogi
    •  & James C.-G. Hombría

  • Article
    | Open Access

    Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

    • Andrew D. Johnston
    • , Claudia A. Simões-Pires
    •  & John M. Greally

  • Article
    | Open Access

    How coronary vessels develop and respond to injury is not fully understood. Here, the authors use murine enhancer:reporter models to identify three transcriptional pathways active in different parts of coronary vasculature. These also contribute to neovascularization in the injured neonatal, but not adult, heart.

    • Sophie Payne
    • , Mala Gunadasa-Rohling
    •  & Sarah De Val

  • Article
    | Open Access

    Histone 3 lysine 79 is mono (me1), di (me2), or tri (me3) methylated by the methyltransferase DOT1L. Here the authors reveal a group of enhancers defined by H3K79me2/3 which regulates enhancer-promoter interactions and other key enhancer features in MLL-AF4 leukemia cells.

    • Laura Godfrey
    • , Nicholas T. Crump
    •  & Thomas A. Milne

  • Article
    | Open Access

    Spatial organization of regulatory elements and its impact on gene expression in plants remain unclear. Here, the authors construct maize chromatin interaction maps using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and show their associations with gene expression and agronomic traits.

    • Yong Peng
    • , Dan Xiong
    •  & Xingwang Li

  • Article
    | Open Access

    Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) can discover specific protein-centered chromatin interactions in high resolution. Here, the authors use ChIA-PET to reveal the complex and dynamic interactions between proximal and distal regulatory regions of genes in maize.

    • En Li
    • , Han Liu
    •  & Jinsheng Lai

  • Article
    | Open Access

    The type II nuclear receptors (NRs) and the retinoid X receptor (RXR) form heterodimeric transcription factors to regulate development, metabolism, and inflammation. Here the authors employ protein-binding microarrays to comprehensively analyze the DNA binding of 12 NR:RXRα heterodimers, and report promiscuous NR-DNA binding.

    • Ashley Penvose
    • , Jessica L. Keenan
    •  & Trevor Siggers

  • Article
    | Open Access

    Although Krüppel-associated box zinc finger proteins (KZFPs) were found to mostly repress transposable elements, recent studies found that KFZPs also play other roles in cells. Here, the authors provide evidence that the KZFP ZFP30 promotes adipogenesis by targeting and activating a retrotransposon-derived Pparg2 enhancer in cooperation with co-regulator KRAB-associated protein 1 (KAP1).

    • Wanze Chen
    • , Petra C. Schwalie
    •  & Bart Deplancke

  • Article
    | Open Access

    Cdk12 is primarily involved in the regulation of DNA damage response (DDR) gene transcription as well as mRNA processing. Here, the authors demonstrate that CDK12 suppresses intronic polyadenylation, and that inhibition of this kinase primarily affects the expression of long genes with higher numbers of polyA sites, features common to many DDR genes.

    • Malgorzata Krajewska
    • , Ruben Dries
    •  & Rani E. George

  • Article
    | Open Access

    CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.

    • Jiao Li
    • , Kaimeng Huang
    •  & Hongjie Yao

  • Article
    | Open Access

    Certain archaea appear to metabolize fatty acids, but the regulation of these pathways is unclear. Here, Wang et al. provide genetic, functional and structural evidence supporting that a TetR-family transcriptional regulator is involved in regulation of fatty acid metabolism in Sulfolobus acidocaldarius.

    • Kun Wang
    • , David Sybers
    •  & Eveline Peeters

  • Article
    | Open Access

    Curaxins are a recently discovered class of anti-cancer agents that disturbs DNA/histone interactions within. Here the authors provide evidence that curaxins affect the spatial genome organization and compromise enhancer-promoter communication necessary for expression of several oncogenes, including MYC.

    • Omar L. Kantidze
    • , Artem V. Luzhin
    •  & Sergey V. Razin

  • Article
    | Open Access

    We know a large number of risk SNPs for schizophrenia, but little about how these SNPs contribute to the disorder. Here, the authors use functional genomics to identify risk SNPs that disrupt transcription factor binding and validate the regulatory effects of the transcription factor binding-disrupting SNPs.

    • Yongxia Huo
    • , Shiwu Li
    •  & Xiong-Jian Luo

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