Bidirectional Transcription Arises from Two Distinct Hubs of Transcription Factor Binding and Active Chromatin.

Abstract:

:Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites (TSSs) near mouse mRNA genes. We find that coupled sense and anti-sense TSSs precisely define the boundaries of a nucleosome-depleted region (NDR) that is highly enriched in transcription factor (TF) motifs. Notably, as the distance between sense and anti-sense TSSs increases, so does the size of the NDR, the level of signal-dependent TF binding, and gene activation. We further discover a group of anti-sense TSSs in macrophages with an enhancer-like chromatin signature. Interestingly, this signature identifies divergent promoters that are activated during immune challenge. We propose that anti-sense promoters serve as platforms for TF binding and establishment of active chromatin to further regulate or enhance sense-strand mRNA expression.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Scruggs BS,Gilchrist DA,Nechaev S,Muse GW,Burkholder A,Fargo DC,Adelman K

doi

10.1016/j.molcel.2015.04.006

subject

Has Abstract

pub_date

2015-06-18 00:00:00

pages

1101-12

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(15)00262-2

journal_volume

58

pub_type

杂志文章
  • Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers.

    abstract::Aberrant folding and fibrillar aggregation by polyglutamine (polyQ) expansion proteins are associated with cytotoxicity in Huntington's disease and other neurodegenerative disorders. Hsp70 chaperones have an inhibitory effect on fibril formation and can alleviate polyQ cytotoxicity. Here we show that the cytosolic cha...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.08.017

    authors: Behrends C,Langer CA,Boteva R,Böttcher UM,Stemp MJ,Schaffar G,Rao BV,Giese A,Kretzschmar H,Siegers K,Hartl FU

    更新日期:2006-09-15 00:00:00

  • Deamidation of Bcl-X(L): a new twist in a genotoxic murder mystery.

    abstract::Bcl-2 proteins are critical regulators of apoptosis following DNA damage. Recent studies have shown that genotoxic stress induces the deamidation of Bcl-X(L), inhibiting its antiapoptotic activities. Remarkably, Rb and p53 are important regulators of this novel modification of Bcl-X(L). ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00693-7

    authors: Johnstone RW

    更新日期:2002-10-01 00:00:00

  • The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1.

    abstract::Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals a...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.05.026

    authors: Flury V,Georgescu PR,Iesmantavicius V,Shimada Y,Kuzdere T,Braun S,Bühler M

    更新日期:2017-07-20 00:00:00

  • Regulation of apoptosis by alternative pre-mRNA splicing.

    abstract::Apoptosis, a phenomenon that allows the regulated destruction and disposal of damaged or unwanted cells, is common to many cellular processes in multicellular organisms. In humans more than 200 proteins are involved in apoptosis, many of which are dysregulated or defective in human diseases including cancer. A large n...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2005.05.026

    authors: Schwerk C,Schulze-Osthoff K

    更新日期:2005-07-01 00:00:00

  • Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.

    abstract::The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chrom...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.01.028

    authors: Nam HJ,Boo K,Kim D,Han DH,Choe HK,Kim CR,Sun W,Kim H,Kim K,Lee H,Metzger E,Schuele R,Yoo SH,Takahashi JS,Cho S,Son GH,Baek SH

    更新日期:2014-03-06 00:00:00

  • VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway.

    abstract::Interference with nucleocytoplasmic transport is a strategy employed by certain viruses to compromise host cellular function. While it has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs, the underlying mechanism has not been fully established. ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.11.023

    authors: Faria PA,Chakraborty P,Levay A,Barber GN,Ezelle HJ,Enninga J,Arana C,van Deursen J,Fontoura BM

    更新日期:2005-01-07 00:00:00

  • Stopping the Clock with MYC.

    abstract::In a recent paper in Cell Metabolism, Altman et al. (2015) report that MYC disrupts the molecular clock in cancer cells and describe a link between oncogenesis, circadian rhythms, and metabolism. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2015.11.008

    authors: Lau AN,Vander Heiden MG

    更新日期:2015-11-19 00:00:00

  • The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.

    abstract::Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic pro...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.12.025

    authors: Evans ML,Chorell E,Taylor JD,Åden J,Götheson A,Li F,Koch M,Sefer L,Matthews SJ,Wittung-Stafshede P,Almqvist F,Chapman MR

    更新日期:2015-02-05 00:00:00

  • Diabetes mutations delineate an atypical POU domain in HNF-1alpha.

    abstract::Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00704-9

    authors: Chi YI,Frantz JD,Oh BC,Hansen L,Dhe-Paganon S,Shoelson SE

    更新日期:2002-11-01 00:00:00

  • Phosphatidic Acid Signals via the Hippo Pathway.

    abstract::In this issue of Molecular Cell, Han et al. (2018) show that phosphatidic acid inhibits the action of the LATS kinases, key mediators of Hippo pathway signaling, which leads to an increase in the nuclear activity of the transcriptional regulator YAP. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.10.004

    authors: Stampouloglou E,Varelas X

    更新日期:2018-10-18 00:00:00

  • Histone methylation by PRC2 is inhibited by active chromatin marks.

    abstract::The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.03.025

    authors: Schmitges FW,Prusty AB,Faty M,Stützer A,Lingaraju GM,Aiwazian J,Sack R,Hess D,Li L,Zhou S,Bunker RD,Wirth U,Bouwmeester T,Bauer A,Ly-Hartig N,Zhao K,Chan H,Gu J,Gut H,Fischle W,Müller J,Thomä NH

    更新日期:2011-05-06 00:00:00

  • Structural basis of Rho GTPase-mediated activation of the formin mDia1.

    abstract::Diaphanous-related formins (DRFs) regulate dynamics of unbranched actin filaments during cell contraction and cytokinesis. DRFs are autoinhibited through intramolecular binding of a Diaphanous autoinhibitory domain (DAD) to a conserved N-terminal regulatory element. Autoinhibition is relieved through binding of the GT...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.04.002

    authors: Otomo T,Otomo C,Tomchick DR,Machius M,Rosen MK

    更新日期:2005-04-29 00:00:00

  • The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5.

    abstract::Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here,...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.09.018

    authors: Sekine Y,Hatanaka R,Watanabe T,Sono N,Iemura S,Natsume T,Kuranaga E,Miura M,Takeda K,Ichijo H

    更新日期:2012-12-14 00:00:00

  • Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.

    abstract::Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue lo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.11.013

    authors: Chen C,Ha BH,Thévenin AF,Lou HJ,Zhang R,Yip KY,Peterson JR,Gerstein M,Kim PM,Filippakopoulos P,Knapp S,Boggon TJ,Turk BE

    更新日期:2014-01-09 00:00:00

  • Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37.

    abstract::Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in bin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.07.021

    authors: Vaughan CK,Mollapour M,Smith JR,Truman A,Hu B,Good VM,Panaretou B,Neckers L,Clarke PA,Workman P,Piper PW,Prodromou C,Pearl LH

    更新日期:2008-09-26 00:00:00

  • Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.

    abstract::Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.12.039

    authors: Sahtoe DD,van Dijk WJ,El Oualid F,Ekkebus R,Ovaa H,Sixma TK

    更新日期:2015-03-05 00:00:00

  • RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability.

    abstract::Genome instability, a hallmark of cancer progression, is thought to arise through DNA double strand breaks (DSBs). Studies in yeast and mammalian cells have shown that DSBs and instability can occur through RNA:DNA hybrids generated by defects in RNA elongation and splicing. We report that in yeast hybrids naturally f...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.10.017

    authors: Wahba L,Amon JD,Koshland D,Vuica-Ross M

    更新日期:2011-12-23 00:00:00

  • No Longer Hidden Secrets of Proton Pumping: The Resolution Revolution Enlightens V-ATPases.

    abstract::In this issue of Molecular Cell, Roh et al. (2018) present a high-resolution cryo-EM structure of the nanodisc-reconstituted yeast Vo proton channel that provides important new insights into subunit arrangements and the proton translocation pathway in V-type ATPases. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.02.031

    authors: Muench SP,van der Laan M

    更新日期:2018-03-15 00:00:00

  • Modulation of transcription affects mRNP quality.

    abstract::Cotranscriptional loading of proteins onto nascent transcripts contributes to the formation of messenger ribonucleoprotein particles (mRNPs) competent for nuclear export. The transcription machinery is believed to play a pivotal role in mRNP assembly, which is at least partially linked to the function of the THO/TREX ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.09.019

    authors: Jensen TH,Boulay J,Olesen JR,Colin J,Weyler M,Libri D

    更新日期:2004-10-22 00:00:00

  • To Cut or Not to Cut: Discovery of a Novel Regulator of DNA Break Resection.

    abstract::Nucleolytic resection of DNA double-strand breaks is the crucial first step in their repair via homologous recombination. New findings by Tkáč et al. (2016) published in this issue of Molecular Cell identify HELB as a novel, cell-cycle-specific negative regulator of DNA end resection. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2016.01.022

    authors: Daley JM,Sung P

    更新日期:2016-02-04 00:00:00

  • Molecular links between centrosome and midbody.

    abstract::The terminal step in cytokinesis that severs a cell in two-abscission-is poorly understood. In Developmental Cell, Fabbro et al (2005) identify a centrosome protein whose multiple phosphorylations regulate its movement from centrosome to midbody and completion of abscission. ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2005.10.010

    authors: Doxsey SJ

    更新日期:2005-10-28 00:00:00

  • Crystal structure of colicin E3: implications for cell entry and ribosome inactivation.

    abstract::Colicins kill E. coli by a process that involves binding to a surface receptor, entering the cell, and, finally, intoxicating it. The lethal action of colicin E3 is a specific cleavage in the ribosomal decoding A site. The crystal structure of colicin E3, reported here in a binary complex with its immunity protein (IP...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00396-3

    authors: Soelaiman S,Jakes K,Wu N,Li C,Shoham M

    更新日期:2001-11-01 00:00:00

  • Frozen in Transcription: Cryo-EM Structures of Pol II Transcribing through a Nucleosome.

    abstract::In a recent publication in Science, Kujirai et al. (2018) use single-particle cryo-EM to resolve several Pol II-nucleosome interactions, shedding new light on transcription elongation in a native chromatin environment. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.11.027

    authors: Noe Gonzalez M,Conaway RC,Conaway JW

    更新日期:2018-12-06 00:00:00

  • Modulation of RNA polymerase assembly dynamics in transcriptional regulation.

    abstract::The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used single-cell fluorescence imaging combined with computational modeling and chr...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.04.021

    authors: Gorski SA,Snyder SK,John S,Grummt I,Misteli T

    更新日期:2008-05-23 00:00:00

  • Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.

    abstract::Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with hom...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00465-3

    authors: Mullen MM,Haan KM,Longnecker R,Jardetzky TS

    更新日期:2002-02-01 00:00:00

  • Toll-like receptors and RNA helicases: two parallel ways to trigger antiviral responses.

    abstract::The early detection by the host of invading microorganisms, including viruses, depends on a limited number of specific receptors that recognize pathogen-associated molecular patterns (PAMPs). A few of these PAMPs, including ssRNA and dsRNA, are recognized by Toll-like receptors (TLR)-7/8 and TLR3, respectively. Activa...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2006.05.012

    authors: Meylan E,Tschopp J

    更新日期:2006-06-09 00:00:00

  • H2AX prevents DNA breaks from progressing to chromosome breaks and translocations.

    abstract::Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks oc...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.01.005

    authors: Franco S,Gostissa M,Zha S,Lombard DB,Murphy MM,Zarrin AA,Yan C,Tepsuporn S,Morales JC,Adams MM,Lou Z,Bassing CH,Manis JP,Chen J,Carpenter PB,Alt FW

    更新日期:2006-01-20 00:00:00

  • Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O.

    abstract::The tumor suppressor BAP1 interacts with chromatin-associated proteins and regulates cell proliferation, but its mechanism of action and regulation remain poorly defined. We show that the ubiquitin-conjugating enzyme UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.03.002

    authors: Mashtalir N,Daou S,Barbour H,Sen NN,Gagnon J,Hammond-Martel I,Dar HH,Therrien M,Affar el B

    更新日期:2014-05-08 00:00:00

  • Membrane Protein Dislocation by the Rhomboid Pseudoprotease Dfm1: No Pore Needed?

    abstract::Defective ER-resident membrane proteins need to be ejected into the cytoplasm in order to be degraded by the proteasome, but the exact mechanism remains unclear. In this issue of Molecular Cell, Neal et al. (2018) reveal that the rhomboid pseudoprotease Dfm1 defines the central ERAD component for membrane protein disl...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2017.12.031

    authors: Avci D,Lemberg MK

    更新日期:2018-01-18 00:00:00

  • Mammalian mirtron genes.

    abstract::Mirtrons are alternative precursors for microRNA biogenesis that were recently described in invertebrates. These short hairpin introns use splicing to bypass Drosha cleavage, which is otherwise essential for the generation of canonical animal microRNAs. Using computational and experimental strategies, we now establish...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.09.028

    authors: Berezikov E,Chung WJ,Willis J,Cuppen E,Lai EC

    更新日期:2007-10-26 00:00:00