A nanobody-based system using fluorescent proteins as scaffolds for cell-specific gene manipulation.


:Fluorescent proteins are commonly used to label cells across organisms, but the unmodified forms cannot control biological activities. Using GFP-binding proteins derived from Camelid antibodies, we co-opted GFP as a scaffold for inducing formation of biologically active complexes, developing a library of hybrid transcription factors that control gene expression only in the presence of GFP or its derivatives. The modular design allows for variation in key properties such as DNA specificity, transcriptional potency, and drug dependency. Production of GFP controlled cell-specific gene expression and facilitated functional perturbations in the mouse retina and brain. Further, retrofitting existing transgenic GFP mouse and zebrafish lines for GFP-dependent transcription enabled applications such as optogenetic probing of neural circuits. This work establishes GFP as a multifunctional scaffold and opens the door to selective manipulation of diverse GFP-labeled cells across transgenic lines. This approach may also be extended to exploit other intracellular products as cell-specific scaffolds in multicellular organisms.






Tang JC,Szikra T,Kozorovitskiy Y,Teixiera M,Sabatini BL,Roska B,Cepko CL




Has Abstract


2013-08-15 00:00:00
















  • HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence.

    abstract::Expression of human immunodeficiency virus type 1 structural proteins requires both the viral Rev trans-activator and its cis-acting RNA target sequence, the Rev response element (RRE). The RRE has been mapped to a conserved region of the HIV-1 env gene and is predicted to form a complex, highly stable RNA stem-loop s...


    pub_type: 杂志文章


    authors: Malim MH,Tiley LS,McCarn DF,Rusche JR,Hauber J,Cullen BR

    更新日期:1990-02-23 00:00:00

  • Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly.

    abstract::Chromatin assembly factor 1 (CAF-1) and Rtt106 participate in the deposition of newly synthesized histones onto replicating DNA to form nucleosomes. This process is critical for the maintenance of genome stability and inheritance of functionally specialized chromatin structures in proliferating cells. However, the mol...


    pub_type: 杂志文章


    authors: Li Q,Zhou H,Wurtele H,Davies B,Horazdovsky B,Verreault A,Zhang Z

    更新日期:2008-07-25 00:00:00

  • Flexible Ion Barrier.

    abstract::The central vasculature of plant roots is protected by a hydrophobic ring of endodermal cells that are enclosed by lamellae of suberin. Barberon et al. demonstrate that endodermal suberization plasticity facilitates ion homeostasis, with antithetical regulation of suberin deposition and degradation by the phytohormone...


    pub_type: 评论,杂志文章


    authors: Pauluzzi G,Bailey-Serres J

    更新日期:2016-01-28 00:00:00

  • TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family.

    abstract::We have cloned and characterized the rat telomerase protein component 1 gene (TLP1), which is related to the gene for Tetrahymena p80. The cDNA encodes a 2629 amino acid sequence and produces the TLP1 proteins p240 and p230. The anti-TLP1 antibody specifically immunoprecipitated the telomerase activity. Moreover, p240...


    pub_type: 杂志文章


    authors: Nakayama J,Saito M,Nakamura H,Matsuura A,Ishikawa F

    更新日期:1997-03-21 00:00:00

  • Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor.

    abstract::The specificity of target gene activation by steroid receptors is encoded within a small, cysteine-rich domain that is believed to form two zinc-coordinated fingers. Here we show that the ability of glucocorticoid and estrogen receptors to discriminate between their closely related response elements resides in the two...


    pub_type: 杂志文章


    authors: Danielsen M,Hinck L,Ringold GM

    更新日期:1989-06-30 00:00:00

  • Beyond the Triplet Code: Context Cues Transform Translation.

    abstract::The elucidation of the genetic code remains among the most influential discoveries in biology. While innumerable studies have validated the general universality of the code and its value in predicting and analyzing protein coding sequences, established and emerging work has also suggested that full genome decryption m...


    pub_type: 杂志文章,评审


    authors: Brar GA

    更新日期:2016-12-15 00:00:00

  • Probing DNA by 2-OG-dependent dioxygenase.

    abstract::TET-mediated 5-methyl cytosine (5mC) oxidation acts in epigenetic regulation, stem cell development, and cancer. Hu et al. now determine the crystal structure of the TET2 catalytic domain bound to DNA, shedding light on 5mC-DNA substrate recognition and the catalytic mechanism of 5mC oxidation. ...


    pub_type: 评论,杂志文章


    authors: Tsai CL,Tainer JA

    更新日期:2013-12-19 00:00:00

  • Trans-activation by HIV-1 Tat via a heterologous RNA binding protein.

    abstract::The HIV-1 trans-activator Tat increases levels of viral gene expression and replication. The target for Tat is an RNA stem-loop called TAR, located at the 5' end of all viral transcripts. To study the mechanism of action and map functional domains of Tat, we fused Tat to the coat protein of bacteriophage MS2, an RNA b...


    pub_type: 杂志文章


    authors: Selby MJ,Peterlin BM

    更新日期:1990-08-24 00:00:00

  • From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II.

    abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...


    pub_type: 杂志文章


    authors: Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJ

    更新日期:2013-08-15 00:00:00

  • The hunger genes: pathways to obesity.

    abstract::The global rise in the prevalence of obesity and associated co-morbidities such as type 2 diabetes, cardiovascular disease, and cancer represents a major public health concern. The biological response to increased consumption of palatable foods or a reduction in energy expenditure is highly variable between individual...


    pub_type: 杂志文章,评审


    authors: van der Klaauw AA,Farooqi IS

    更新日期:2015-03-26 00:00:00

  • Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration.

    abstract::E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-...


    pub_type: 杂志文章


    authors: Cai D,Chen SC,Prasad M,He L,Wang X,Choesmel-Cadamuro V,Sawyer JK,Danuser G,Montell DJ

    更新日期:2014-05-22 00:00:00

  • The president's scientist.

    abstract::The science advisor to the US president has the opportunity to influence how scientific research is supported by the federal government, as well as the ways in which science and technology can be applied to meet the needs of society. ...


    pub_type: 杂志文章


    authors: Lane NF,Matthews KR

    更新日期:2009-11-25 00:00:00

  • The nucleotide sequence of the maize controlling element Activator.

    abstract::We have determined the nucleotide sequence of the transposable maize controlling element Activator (Ac). The Ac element is 4563 bp long and has an imperfect terminal repetition of 11 bp. The element contains two open reading frames (ORF) encoding polypeptides of 839 and 210 amino acids. Evidence derived from structura...


    pub_type: 杂志文章


    authors: Pohlman RF,Fedoroff NV,Messing J

    更新日期:1984-06-01 00:00:00

  • Epigenetics drives RAGs to recombination riches.

    abstract::V(D)J recombination of antigen receptor gene segments in B and T cells is mediated by the lymphoid-specific proteins RAG1 and RAG2. Now, Ji et al. (2010) demonstrate how RAG1 and RAG2 use DNA sequence specificity and modified histones within chromatin to target specific loci for V(D)J recombination at different stages...


    pub_type: 评论,杂志文章


    authors: Schlissel MS

    更新日期:2010-04-30 00:00:00

  • Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression.

    abstract::Major depressive disorder (MDD) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. Separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depre...


    pub_type: 杂志文章


    authors: Knowland D,Lilascharoen V,Pacia CP,Shin S,Wang EH,Lim BK

    更新日期:2017-07-13 00:00:00

  • Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons.

    abstract::The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with either short or long 3' untranslated regions (3' UTRs). The physiological significance of the two forms of mRNAs encoding the same protein is unknown. Here, we show that the short and long 3' UTR BDNF mRNAs are involved in different cell...


    pub_type: 杂志文章


    authors: An JJ,Gharami K,Liao GY,Woo NH,Lau AG,Vanevski F,Torre ER,Jones KR,Feng Y,Lu B,Xu B

    更新日期:2008-07-11 00:00:00

  • Cooperativity in transactivation between retinoic acid receptor and TFIID requires an activity analogous to E1A.

    abstract::In embryonal carcinoma (EC) cells retinoic acid (RA) strongly induces transcription from the RA receptor beta 2 (RAR beta 2) promoter through an RA response element (RARE) located in close proximity to the TATA box. Here we demonstrate that recombinant human TATA box-binding protein, hTFIID, and RAR functionally coope...


    pub_type: 杂志文章


    authors: Berkenstam A,Vivanco Ruiz MM,Barettino D,Horikoshi M,Stunnenberg HG

    更新日期:1992-05-01 00:00:00

  • The Interfaces of Genetic Conflict Are Hot Spots for Innovation.

    abstract::RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for th...


    pub_type: 评论,杂志文章


    authors: Carter J,Hoffman C,Wiedenheft B

    更新日期:2017-01-12 00:00:00

  • Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7.

    abstract::Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restr...


    pub_type: 杂志文章


    authors: Bremner R,Balmain A

    更新日期:1990-05-04 00:00:00

  • Monoculture breeds poor social skills.

    abstract::Two studies from Jarosz et al. describe how [GAR(+)], a protein-based epigenetic determinant found mainly in wild yeast strains, can be activated by microbial cross-kingdom communication. With the aid of genetically and ecologically diverse bacteria, yeast can override an ancient regulatory mechanism of glucose repres...


    pub_type: 评论,杂志文章


    authors: Staniforth GL,Tuite MF

    更新日期:2014-08-28 00:00:00

  • The effect of X chromosome heterozygosity on the structure of the ribosomal genes in Drosophila melanogaster.

    abstract::Sucrose gradient analysis of DNA isolated from detergent-pronase lysates of adult flies has been used to look for ribosomal genes not integrated into the DNA of the chromosome in genotypes containing various combinations of inversions having breakpoints in the proximal heterochromatin of the X chromosome. Unintegrated...


    pub_type: 杂志文章


    authors: Harford AG,Zuchowski CI

    更新日期:1977-06-01 00:00:00

  • BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.

    abstract::BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. A BACH1 derivative, bearing a mutation in a residue that was essential for catalytic function in other helicases, interfered with normal double-strand break repair in a manner t...


    pub_type: 杂志文章


    authors: Cantor SB,Bell DW,Ganesan S,Kass EM,Drapkin R,Grossman S,Wahrer DC,Sgroi DC,Lane WS,Haber DA,Livingston DM

    更新日期:2001-04-06 00:00:00

  • Antisense RNA inhibits expression of membrane skeleton protein 4.1 during embryonic development of Xenopus.

    abstract::Plasmids expressing partial-length sense or antisense protein 4.1 RNA were microinjected into fertilized Xenopus eggs. Nuclease protection assays reveal that antisense protein 4.1 RNA lead to the specific loss of endogenous protein 4.1 transcripts after midblastula transition, with no effect on the levels of three unr...


    pub_type: 杂志文章


    authors: Giebelhaus DH,Eib DW,Moon RT

    更新日期:1988-05-20 00:00:00

  • Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.

    abstract::The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on t...


    pub_type: 杂志文章


    authors: Symons M,Derry JM,Karlak B,Jiang S,Lemahieu V,Mccormick F,Francke U,Abo A

    更新日期:1996-03-08 00:00:00

  • The bacterial effector VopL organizes actin into filament-like structures.

    abstract::VopL is an effector protein from Vibrio parahaemolyticus that nucleates actin filaments. VopL consists of a VopL C-terminal domain (VCD) and an array of three WASP homology 2 (WH2) motifs. Here, we report the crystal structure of the VCD dimer bound to actin. The VCD organizes three actin monomers in a spatial arrange...


    pub_type: 杂志文章


    authors: Zahm JA,Padrick SB,Chen Z,Pak CW,Yunus AA,Henry L,Tomchick DR,Chen Z,Rosen MK

    更新日期:2013-10-10 00:00:00

  • Biochemical fractionation and assembly of the membrane components that mediate nascent chain targeting and translocation.

    abstract::Fractionation of a microsomal detergent extract with ammonium sulfate allows separation of the signal recognition particle receptor (SR alpha), which is required for targeting of the nascent chain, from other microsomal proteins, such as signal peptidase, whose activity is displayed during subsequent translocation. Th...


    pub_type: 杂志文章


    authors: Nicchitta CV,Migliaccio G,Blobel G

    更新日期:1991-05-17 00:00:00

  • Autophagosome precursor maturation requires homotypic fusion.

    abstract::Autophagy is a catabolic process in which lysosomes degrade intracytoplasmic contents transported in double-membraned autophagosomes. Autophagosomes are formed by the elongation and fusion of phagophores, which can be derived from preautophagosomal structures coming from the plasma membrane and other sites like the en...


    pub_type: 杂志文章


    authors: Moreau K,Ravikumar B,Renna M,Puri C,Rubinsztein DC

    更新日期:2011-07-22 00:00:00

  • A Single Transcription Factor Drives Toxoplasma gondii Differentiation.

    abstract::Microbes that cause persistent infections (e.g., herpes viruses) do so by switching from fast-growing lytic states to slow-growing latent states. Waldman et al. have identified a single transcription factor that governs the switch between the lytic and latent forms of Toxoplasma gondii, a parasite that causes a persis...


    pub_type: 评论,杂志文章


    authors: Kochanowsky JA,Koshy AA

    更新日期:2020-01-23 00:00:00

  • DNAase I sensitivity and methylation of active versus inactive rRNA genes in xenopus species hybrids.

    abstract::We studied the chromatin structure and methylation of ribosomal RNA genes (rDNA) in hybrids between Xenopus laevis and Xenopus borealis. S1-nuclease protection experiments showed that 97%-98% of the rRNA precursor in hybrid tadpoles was of the X. laevis type. Preferential expression of the laevis rDNA was correlated w...


    pub_type: 杂志文章


    authors: Macleod D,Bird A

    更新日期:1982-05-01 00:00:00

  • A DNA-dependent protease involved in DNA-protein crosslink repair.

    abstract::Toxic DNA-protein crosslinks (DPCs) arise by ionizing irradiation and UV light, are particularly caused by endogenously produced reactive compounds such as formaldehyde, and also occur during compromised topoisomerase action. Although nucleotide excision repair and homologous recombination contribute to cell survival ...


    pub_type: 杂志文章


    authors: Stingele J,Schwarz MS,Bloemeke N,Wolf PG,Jentsch S

    更新日期:2014-07-17 00:00:00