P-TEFb, the super elongation complex and mediator regulate a subset of non-paused genes during early Drosophila embryo development.

Abstract:

:Positive Transcription Elongation Factor b (P-TEFb) is a kinase consisting of Cdk9 and Cyclin T that releases RNA Polymerase II (Pol II) into active elongation. It can assemble into a larger Super Elongation Complex (SEC) consisting of additional elongation factors. Here, we use a miRNA-based approach to knock down the maternal contribution of P-TEFb and SEC components in early Drosophila embryos. P-TEFb or SEC depletion results in loss of cells from the embryo posterior and in cellularization defects. Interestingly, the expression of many patterning genes containing promoter-proximal paused Pol II is relatively normal in P-TEFb embryos. Instead, P-TEFb and SEC are required for expression of some non-paused, rapidly transcribed genes in pre-cellular embryos, including the cellularization gene Serendipity-α. We also demonstrate that another P-TEFb regulated gene, terminus, has an essential function in embryo development. Similar morphological and gene expression phenotypes were observed upon knock down of Mediator subunits, providing in vivo evidence that P-TEFb, the SEC and Mediator collaborate in transcription control. Surprisingly, P-TEFb depletion does not affect the ratio of Pol II at the promoter versus the 3' end, despite affecting global Pol II Ser2 phosphorylation levels. Instead, Pol II occupancy is reduced at P-TEFb down-regulated genes. We conclude that a subset of non-paused, pre-cellular genes are among the most susceptible to reduced P-TEFb, SEC and Mediator levels in Drosophila embryos.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Dahlberg O,Shilkova O,Tang M,Holmqvist PH,Mannervik M

doi

10.1371/journal.pgen.1004971

subject

Has Abstract

pub_date

2015-02-13 00:00:00

pages

e1004971

issue

2

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-14-01438

journal_volume

11

pub_type

杂志文章
  • Dual functions of ASCIZ in the DNA base damage response and pulmonary organogenesis.

    abstract::Zn²(+)-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn²(+)-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001170

    authors: Jurado S,Smyth I,van Denderen B,Tenis N,Hammet A,Hewitt K,Ng JL,McNees CJ,Kozlov SV,Oka H,Kobayashi M,Conlan LA,Cole TJ,Yamamoto K,Taniguchi Y,Takeda S,Lavin MF,Heierhorst J

    更新日期:2010-10-21 00:00:00

  • Role of Pirh2 in mediating the regulation of p53 and c-Myc.

    abstract::Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in r...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002360

    authors: Hakem A,Bohgaki M,Lemmers B,Tai E,Salmena L,Matysiak-Zablocki E,Jung YS,Karaskova J,Kaustov L,Duan S,Madore J,Boutros P,Sheng Y,Chesi M,Bergsagel PL,Perez-Ordonez B,Mes-Masson AM,Penn L,Squire J,Chen X,Jurisica I

    更新日期:2011-11-01 00:00:00

  • TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF.

    abstract::Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation u...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006636

    authors: Seberg HE,Van Otterloo E,Loftus SK,Liu H,Bonde G,Sompallae R,Gildea DE,Santana JF,Manak JR,Pavan WJ,Williams T,Cornell RA

    更新日期:2017-03-01 00:00:00

  • Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection.

    abstract::Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this di...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004518

    authors: Turner KH,Everett J,Trivedi U,Rumbaugh KP,Whiteley M

    更新日期:2014-07-24 00:00:00

  • C. elegans CLASP/CLS-2 negatively regulates membrane ingression throughout the oocyte cortex and is required for polar body extrusion.

    abstract::The requirements for oocyte meiotic cytokinesis during polar body extrusion are not well understood. In particular, the relationship between the oocyte meiotic spindle and polar body contractile ring dynamics remains largely unknown. We have used live cell imaging and spindle assembly defective mutants lacking the fun...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008751

    authors: Schlientz AJ,Bowerman B

    更新日期:2020-10-07 00:00:00

  • Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation.

    abstract::Conjugation is one mechanism for intra- and inter-species horizontal gene transfer among bacteria. Conjugative elements have been instrumental in many bacterial species to face the threat of antibiotics, by allowing them to evolve and adapt to these hostile conditions. Conjugative plasmids are transferred to plasmidle...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001165

    authors: Baharoglu Z,Bikard D,Mazel D

    更新日期:2010-10-21 00:00:00

  • Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing.

    abstract::Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of "modular...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0010034

    authors: Xing Y,Lee CJ

    更新日期:2005-09-01 00:00:00

  • Evolution of the Auxin Response Factors from charophyte ancestors.

    abstract::Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition. Auxin Response Factors (ARFs) Transcription Factors (TFs) that mediate auxin-dependent transcriptional changes are divid...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008400

    authors: Martin-Arevalillo R,Thévenon E,Jégu F,Vinos-Poyo T,Vernoux T,Parcy F,Dumas R

    更新日期:2019-09-25 00:00:00

  • The ABI4-induced Arabidopsis ANAC060 transcription factor attenuates ABA signaling and renders seedlings sugar insensitive when present in the nucleus.

    abstract::Seedling establishment is inhibited on media containing high levels (∼ 6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a qua...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004213

    authors: Li P,Zhou H,Shi X,Yu B,Zhou Y,Chen S,Wang Y,Peng Y,Meyer RC,Smeekens SC,Teng S

    更新日期:2014-03-13 00:00:00

  • Hypomorphic mutation of the mouse Huntington's disease gene orthologue.

    abstract::Rare individuals with inactivating mutations in the Huntington's disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ1...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007765

    authors: Murthy V,Tebaldi T,Yoshida T,Erdin S,Calzonetti T,Vijayvargia R,Tripathi T,Kerschbamer E,Seong IS,Quattrone A,Talkowski ME,Gusella JF,Georgopoulos K,MacDonald ME,Biagioli M

    更新日期:2019-03-21 00:00:00

  • H3K27me3 profiling of the endosperm implies exclusion of polycomb group protein targeting by DNA methylation.

    abstract::Polycomb group (PcG) proteins act as evolutionary conserved epigenetic mediators of cell identity because they repress transcriptional programs that are not required at particular developmental stages. Each tissue is likely to have a specific epigenetic profile, which acts as a blueprint for its developmental fate. A ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001152

    authors: Weinhofer I,Hehenberger E,Roszak P,Hennig L,Köhler C

    更新日期:2010-10-07 00:00:00

  • Lymphotoxin-alpha gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study.

    abstract::Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the immune system and local inflammatory response. LTA is expressed in atherosclerotic plaques and has been implicated in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Polymorphisms in the gene encoding lymph...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0020107

    authors: Clarke R,Xu P,Bennett D,Lewington S,Zondervan K,Parish S,Palmer A,Clark S,Cardon L,Peto R,Lathrop M,Collins R,International Study of Infarct Survival (ISIS) Collaborators.

    更新日期:2006-07-01 00:00:00

  • A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells.

    abstract::MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002054

    authors: Zheng GX,Ravi A,Calabrese JM,Medeiros LA,Kirak O,Dennis LM,Jaenisch R,Burge CB,Sharp PA

    更新日期:2011-05-01 00:00:00

  • The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse.

    abstract::Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004924

    authors: Chow CY,Wang X,Riccardi D,Wolfner MF,Clark AG

    更新日期:2015-02-04 00:00:00

  • Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension.

    abstract::High glucose diets are unhealthy, although the mechanisms by which elevated glucose is harmful to whole animal physiology are not well understood. In Caenorhabditis elegans, high glucose shortens lifespan, while chemically inflicted glucose restriction promotes longevity. We investigated the impact of glucose metaboli...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008982

    authors: Onken B,Kalinava N,Driscoll M

    更新日期:2020-08-25 00:00:00

  • Extensive DNA end processing by exo1 and sgs1 inhibits break-induced replication.

    abstract::Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in ext...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001007

    authors: Marrero VA,Symington LS

    更新日期:2010-07-08 00:00:00

  • Only one isoform of Drosophila melanogaster CTP synthase forms the cytoophidium.

    abstract::CTP synthase is an essential enzyme that plays a key role in energy metabolism. Several independent studies have demonstrated that CTP synthase can form an evolutionarily conserved subcellular structure termed cytoophidium. In budding yeast, there are two isoforms of CTP synthase and both isoforms localize in cytoophi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003256

    authors: Azzam G,Liu JL

    更新日期:2013-01-01 00:00:00

  • Ubiquitous polygenicity of human complex traits: genome-wide analysis of 49 traits in Koreans.

    abstract::Recent studies in population of European ancestry have shown that 30% ~ 50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proport...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003355

    authors: Yang J,Lee T,Kim J,Cho MC,Han BG,Lee JY,Lee HJ,Cho S,Kim H

    更新日期:2013-01-01 00:00:00

  • Understanding gene sequence variation in the context of transcription regulation in yeast.

    abstract::DNA sequence polymorphism in a regulatory protein can have a widespread transcriptional effect. Here we present a computational approach for analyzing modules of genes with a common regulation that are affected by specific DNA polymorphisms. We identify such regulatory-linkage modules by integrating genotypic and expr...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000800

    authors: Gat-Viks I,Meller R,Kupiec M,Shamir R

    更新日期:2010-01-01 00:00:00

  • Zinc finger independent genome-wide binding of Sp2 potentiates recruitment of histone-fold protein Nf-y distinguishing it from Sp1 and Sp3.

    abstract::Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-termina...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005102

    authors: Völkel S,Stielow B,Finkernagel F,Stiewe T,Nist A,Suske G

    更新日期:2015-03-20 00:00:00

  • Identification of the master sex determining gene in Northern pike (Esox lucius) reveals restricted sex chromosome differentiation.

    abstract::Teleost fishes, thanks to their rapid evolution of sex determination mechanisms, provide remarkable opportunities to study the formation of sex chromosomes and the mechanisms driving the birth of new master sex determining (MSD) genes. However, the evolutionary interplay between the sex chromosomes and the MSD genes t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008013

    authors: Pan Q,Feron R,Yano A,Guyomard R,Jouanno E,Vigouroux E,Wen M,Busnel JM,Bobe J,Concordet JP,Parrinello H,Journot L,Klopp C,Lluch J,Roques C,Postlethwait J,Schartl M,Herpin A,Guiguen Y

    更新日期:2019-08-22 00:00:00

  • Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation.

    abstract::Elg1, the major subunit of a Replication Factor C-like complex, is critical to ensure genomic stability during DNA replication, and is implicated in controlling chromatin structure. We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication. Measurement of Okazak...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007783

    authors: Gali VK,Dickerson D,Katou Y,Fujiki K,Shirahige K,Owen-Hughes T,Kubota T,Donaldson AD

    更新日期:2018-11-12 00:00:00

  • Binary addition in a living cell based on riboregulation.

    abstract::Synthetic biology aims at (re-)programming living cells like computers to perform new functions for a variety of applications. Initial work rested on transcription factors, but regulatory RNAs have recently gained much attention due to their high programmability. However, functional circuits mainly implemented with re...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007548

    authors: Rosado A,Cordero T,Rodrigo G

    更新日期:2018-07-19 00:00:00

  • Robust demographic inference from genomic and SNP data.

    abstract::We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other curre...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003905

    authors: Excoffier L,Dupanloup I,Huerta-Sánchez E,Sousa VC,Foll M

    更新日期:2013-10-01 00:00:00

  • Marine environmental DNA biomonitoring reveals seasonal patterns in biodiversity and identifies ecosystem responses to anomalous climatic events.

    abstract::Marine ecosystems are changing rapidly as the oceans warm and become more acidic. The physical factors and the changes to ocean chemistry that they drive can all be measured with great precision. Changes in the biological composition of communities in different ocean regions are far more challenging to measure because...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007943

    authors: Berry TE,Saunders BJ,Coghlan ML,Stat M,Jarman S,Richardson AJ,Davies CH,Berry O,Harvey ES,Bunce M

    更新日期:2019-02-08 00:00:00

  • Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation.

    abstract::The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks. Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postnatal repro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005375

    authors: Mould AW,Morgan MA,Nelson AC,Bikoff EK,Robertson EJ

    更新日期:2015-07-09 00:00:00

  • Cytoneme-mediated signaling essential for tumorigenesis.

    abstract::Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor model...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008415

    authors: Fereres S,Hatori R,Hatori M,Kornberg TB

    更新日期:2019-09-30 00:00:00

  • XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways.

    abstract::Loss of the XPF-ERCC1 endonuclease causes a dramatic phenotype that results in progeroid features associated with liver, kidney and bone marrow dysfunction. As this nuclease is involved in multiple DNA repair transactions, it is plausible that this severe phenotype results from the simultaneous inactivation of both br...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008555

    authors: Mulderrig L,Garaycoechea JI

    更新日期:2020-04-09 00:00:00

  • Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.

    abstract::We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-car...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000291

    authors: Windbichler N,Papathanos PA,Crisanti A

    更新日期:2008-12-01 00:00:00

  • Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis.

    abstract::Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004713

    authors: Stine RR,Greenspan LJ,Ramachandran KV,Matunis EL

    更新日期:2014-11-06 00:00:00