Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription.

Abstract:

:Cascades of zygotic gene expression pattern the anterior-posterior (AP) and dorsal-ventral (DV) axes of the early Drosophila embryo. Here, we used the global run-on sequencing assay (GRO-seq) to map the genome-wide RNA polymerase distribution during early Drosophila embryogenesis, thus providing insights into how genes are regulated. We identify widespread promoter-proximal pausing yet show that the presence of paused polymerase does not necessarily equate to direct regulation through pause release to productive elongation. Our data reveal that a subset of early Zelda-activated genes is regulated at the level of polymerase recruitment, whereas other Zelda target and axis patterning genes are predominantly regulated through pause release. In contrast to other signaling pathways, we found that bone morphogenetic protein (BMP) target genes are collectively more highly paused than BMP pathway components and show that BMP target gene expression requires the pause-inducing negative elongation factor (NELF) complex. Our data also suggest that polymerase pausing allows plasticity in gene activation throughout embryogenesis, as transiently repressed and transcriptionally silenced genes maintain and lose promoter polymerases, respectively. Finally, we provide evidence that the major effect of pausing is on the levels, rather than timing, of transcription. These data are discussed in terms of the efficiency of transcriptional activation required across cell populations during developmental time constraints.

journal_name

Genes Dev

journal_title

Genes & development

authors

Saunders A,Core LJ,Sutcliffe C,Lis JT,Ashe HL

doi

10.1101/gad.215459.113

subject

Has Abstract

pub_date

2013-05-15 00:00:00

pages

1146-58

issue

10

eissn

0890-9369

issn

1549-5477

pii

27/10/1146

journal_volume

27

pub_type

杂志文章
  • N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma.

    abstract::Studying the early stages of cancer can provide important insight into the molecular basis of the disease. We identified a preneoplastic stage in the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma. Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1759909

    authors: Kessler JD,Hasegawa H,Brun SN,Emmenegger BA,Yang ZJ,Dutton JW,Wang F,Wechsler-Reya RJ

    更新日期:2009-01-15 00:00:00

  • Tango7 directs cellular remodeling by the Drosophila apoptosome.

    abstract::It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. Here we report that Tango7 collaborates with the Dro...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.219287.113

    authors: D'Brot A,Chen P,Vaishnav M,Yuan S,Akey CW,Abrams JM

    更新日期:2013-08-01 00:00:00

  • The cAMP receptor CAR4 regulates axial patterning and cellular differentiation during late development of Dictyostelium.

    abstract::Pseudoplasmodia of developing Dictyostelium are organized with anteroposterior polarity. We have isolated CAR4, the gene for a new cell-surface, G protein-linked cAMP receptor. CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination. CAR4 is maximally expressed in pseudoplas...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.17.2086

    authors: Louis JM,Ginsburg GT,Kimmel AR

    更新日期:1994-09-01 00:00:00

  • Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity.

    abstract::How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.187807.112

    authors: Anderson C,Williams VC,Moyon B,Daubas P,Tajbakhsh S,Buckingham ME,Shiroishi T,Hughes SM,Borycki AG

    更新日期:2012-09-15 00:00:00

  • RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E.

    abstract::Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.990802

    authors: Kennerdell JR,Yamaguchi S,Carthew RW

    更新日期:2002-08-01 00:00:00

  • The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast grr1p.

    abstract::Genetic analysis in Arabidopsis has led to the identification of several genes that are required for auxin response. One of these genes, AXR1, encodes a protein related to yeast Aos1p, a protein that functions to activate the ubiquitin-related protein Smt3p. Here we report the identification of a new gene called TRANS...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.2.198

    authors: Ruegger M,Dewey E,Gray WM,Hobbie L,Turner J,Estelle M

    更新日期:1998-01-15 00:00:00

  • Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma.

    abstract::The transformer-2 (tra-2) gene of Drosophila melanogaster plays essential roles in both sexual differentiation in the female soma and spermatogenesis in the male germ line. In the female soma, tra-2 is known to act with other genes in the sex determination regulatory cascade to control the sex-specific alternative spl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.5.789

    authors: Mattox W,Palmer MJ,Baker BS

    更新日期:1990-05-01 00:00:00

  • Functional domains of the yeast transcription/replication factor MCM1.

    abstract::MCM1 is an essential yeast DNA-binding protein that affects both minichromosome maintenance, in a manner suggesting that it has DNA replication initiation function, and gene expression. It activates alpha-specific genes together with MAT alpha 1, and represses a-specific genes together with MAT alpha 2. Alone, MCM1 ca...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.5.5.751

    authors: Christ C,Tye BK

    更新日期:1991-05-01 00:00:00

  • The efficiency of RNA 3'-end formation is determined by the distance between the cap site and the poly(A) site in spleen necrosis virus.

    abstract::The efficiency of RNA 3'-end formation of spleen necrosis virus (SNV) is determined by the distance between the cap site and the poly(A) site. When the distance between the cap site and the poly(A) site was shorter than 500 bases, only 3-9% of the RNA was polyadenylated at the SNV poly(A) site. However, when the dista...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.12b.2299

    authors: Iwasaki K,Temin HM

    更新日期:1990-12-01 00:00:00

  • Cytokine rescue of p53-dependent apoptosis and cell cycle arrest is mediated by distinct Jak kinase signaling pathways.

    abstract::Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53-dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.8.1099

    authors: Quelle FW,Wang J,Feng J,Wang D,Cleveland JL,Ihle JN,Zambetti GP

    更新日期:1998-04-15 00:00:00

  • Fragile X-related protein and VIG associate with the RNA interference machinery.

    abstract::RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Dro...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1025202

    authors: Caudy AA,Myers M,Hannon GJ,Hammond SM

    更新日期:2002-10-01 00:00:00

  • The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.

    abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1823109

    authors: Kobayashi T,Mizuno H,Imayoshi I,Furusawa C,Shirahige K,Kageyama R

    更新日期:2009-08-15 00:00:00

  • MT1-MMP regulates the PI3Kδ·Mi-2/NuRD-dependent control of macrophage immune function.

    abstract::Macrophages play critical roles in events ranging from host defense to obesity and cancer, where they infiltrate affected tissues and orchestrate immune responses in tandem with the remodeling of the extracellular matrix (ECM). Despite the dual roles played by macrophages in inflammation, the functions of macrophage-d...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.178749.111

    authors: Shimizu-Hirota R,Xiong W,Baxter BT,Kunkel SL,Maillard I,Chen XW,Sabeh F,Liu R,Li XY,Weiss SJ

    更新日期:2012-02-15 00:00:00

  • Drosophila lacking microRNA miR-278 are defective in energy homeostasis.

    abstract::The mechanisms that control energy homeostasis and tissue growth during development are closely linked through the insulin signal transduction pathway. Changes in the level of insulin and other hormones reflect the nutritional status of the animal to control circulating sugar levels and fat metabolism. Systemic defect...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.374406

    authors: Teleman AA,Maitra S,Cohen SM

    更新日期:2006-02-15 00:00:00

  • An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity.

    abstract::E2F is a cellular, sequence-specific DNA-binding factor that binds to pairs of sites that occur upstream of the E1A and E2 early mRNA cap sites. During adenovirus infection, there is induction of a form of E2F that binds cooperatively to the pair of sites in the E2 control region. Production of the infection-specific ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.7.1062

    authors: Hardy S,Engel DA,Shenk T

    更新日期:1989-07-01 00:00:00

  • 3D reconstruction of the Mu transposase and the Type 1 transpososome: a structural framework for Mu DNA transposition.

    abstract::Mu DNA transposition proceeds through a series of higher-order nucleoprotein complexes called transpososomes. The structural core of the transpososome is a tetramer of the transposase, Mu A, bound to the two transposon ends. High-resolution structural analysis of the intact transposase and the transpososome has not be...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1291405

    authors: Yuan JF,Beniac DR,Chaconas G,Ottensmeyer FP

    更新日期:2005-04-01 00:00:00

  • The loss of circadian PAR bZip transcription factors results in epilepsy.

    abstract::DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.301404

    authors: Gachon F,Fonjallaz P,Damiola F,Gos P,Kodama T,Zakany J,Duboule D,Petit B,Tafti M,Schibler U

    更新日期:2004-06-15 00:00:00

  • Pcf11 orchestrates transcription termination pathways in yeast.

    abstract::In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.251470.114

    authors: Grzechnik P,Gdula MR,Proudfoot NJ

    更新日期:2015-04-15 00:00:00

  • The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss.

    abstract::The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot mutation in human cancer. p53 homozygous mutant mice have unstable mutant p53 in normal cells and stabilize mutant p53 in some...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1662908

    authors: Terzian T,Suh YA,Iwakuma T,Post SM,Neumann M,Lang GA,Van Pelt CS,Lozano G

    更新日期:2008-05-15 00:00:00

  • pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.

    abstract::Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX,...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.8.1217

    authors: Haviv I,Matza Y,Shaul Y

    更新日期:1998-04-15 00:00:00

  • Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.

    abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.318675.118

    authors: Inoue A,Chen Z,Yin Q,Zhang Y

    更新日期:2018-12-01 00:00:00

  • The interplay between multiple enhancer and silencer elements defines the pattern of decapentaplegic expression.

    abstract::The product of the zygotically active decapentaplegic (dpp) gene appears to function as a morphogen that specifies positional information in the dorsal half of the Drosophila embryo. The dorsal-specific transcription of dpp is the key step in establishing a morphogen gradient. We demonstrate here that multiple regions...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.4.694

    authors: Huang JD,Schwyter DH,Shirokawa JM,Courey AJ

    更新日期:1993-04-01 00:00:00

  • A novel role for the 3' region of introns in pre-mRNA splicing of Saccharomyces cerevisiae.

    abstract::To investigate the importance of sequences between the yeast (Saccharomyces cerevisiae) branch point (TACTAAC box) and 3' splice site (AG), we generated a series of pre-mRNA substrates that differed in the length of RNA retained on the 3' side of the TACTAAC box. These pre-mRNAs were compared as substrates for the fir...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1.3.238

    authors: Rymond BC,Torrey DD,Rosbash M

    更新日期:1987-05-01 00:00:00

  • Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei.

    abstract::Unusually for a eukaryote, genes transcribed by RNA polymerase II (pol II) in Trypanosoma brucei are arranged in polycistronic transcription units. With one exception, no pol II promoter motifs have been identified, and how transcription is initiated remains an enigma. T. brucei has four histone variants: H2AZ, H2BV, ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1790409

    authors: Siegel TN,Hekstra DR,Kemp LE,Figueiredo LM,Lowell JE,Fenyo D,Wang X,Dewell S,Cross GA

    更新日期:2009-05-01 00:00:00

  • Genomic instability and endoreduplication triggered by RAD17 deletion.

    abstract::Cell cycle checkpoints are critical for genomic stability. Rad17, a component of the checkpoint clamp loader complex (Rad17/Rfc2-5), is required for the response to DNA damage and replication stress. To explore the role of Rad17 in the maintenance of genomic integrity, we established somatic conditional alleles of RAD...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1065103

    authors: Wang X,Zou L,Zheng H,Wei Q,Elledge SJ,Li L

    更新日期:2003-04-15 00:00:00

  • The excess microsporocytes1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther.

    abstract::Cell differentiation is essential for the development of multicellular organisms. In flowering plants, the haploid male gametophytes (pollen grains) are generated in the anther from reproductive cells called microsporocytes. Several types of somatic cells ensure successful pollen development, and thus reproduction. Ho...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.997902

    authors: Zhao DZ,Wang GF,Speal B,Ma H

    更新日期:2002-08-01 00:00:00

  • Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine.

    abstract::Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activitie...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.271130.115

    authors: Cheung EC,Lee P,Ceteci F,Nixon C,Blyth K,Sansom OJ,Vousden KH

    更新日期:2016-01-01 00:00:00

  • Intercellular C-signaling in Myxococcus xanthus involves a branched signal transduction pathway.

    abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.6.740

    authors: Søgaard-Andersen L,Slack FJ,Kimsey H,Kaiser D

    更新日期:1996-03-15 00:00:00

  • RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs.

    abstract::Most eukaryotic mRNAs are translated using a cap-dependent mechanism of translation. However, approximately 10% of mammalian mRNAs initiate translation using a cap-independent mechanism that is not well understood. These mRNAs contain an internal ribosome entry site (IRES) located in the 5' untranslated region. The cr...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1832209

    authors: Landry DM,Hertz MI,Thompson SR

    更新日期:2009-12-01 00:00:00

  • p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex.

    abstract::The generation of neurons by progenitor cells involves the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation, and cell migration. The mechanisms that integrate these different events into a coherent developmental program are not well understood. Here ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.377106

    authors: Nguyen L,Besson A,Heng JI,Schuurmans C,Teboul L,Parras C,Philpott A,Roberts JM,Guillemot F

    更新日期:2006-06-01 00:00:00